Article Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.

Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.

The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated.

PDF (5 MB)

SUBJECTS:

Get e-Alerts

Biography

Omar Boutureira was born in Tarragona, Spain, in 1979. He studied Chemistry at the Universitat Rovira i Virgili (URV) and received his B.Sc. in 2002 and Ph.D. in 2007 under the supervision of Prof. Sergio Castillón. After postdoctoral research as a Marie Curie Fellow with Prof. Benjamin G. Davis at the University of Oxford, U.K., he returned in 2011 to URV as an Assistant Professor. At URV he is supported by Juan de la Cierva and Marie Curie CIG fellowships. His research interests focus on various aspects of Chemical Biology and Glycobiology including chemical protein modification and the use of halogens and chalcogens as well as metal-mediated strategies in glycoconjugate synthesis and carbohydrate chemistry.

Biography

Gonçalo Bernardes is a Group Leader at the University of Cambridge, U.K. He is also Director of the Chemical Biology and Pharmaceutical Biotechnology Unit at the Instituto de Medicina Molecular, Portugal. After completing his D.Phil. degree in 2008 at the University of Oxford, U.K., he undertook postdoctoral work at the Max-Planck Institute of Colloids and Interfaces, Germany, and the ETH Zürich, Switzerland, and worked as a Group Leader at Alfama Lda, Portugal. His research group interests focus on the development of new chemical site-selective protein modification reactions for basic biology and drug development.

1 Introduction

ARTICLE SECTIONS

Jump To

Chemical protein modification has emerged as an invaluable tool for the development of modified proteins. The complementary use of both genetic and chemical methods has provided a large toolbox that allows the preparation of almost unlimited protein constructs with either natural or synthetically modified residues.(1) Such a protein chemodiversity, usually achieved after translation and commonly referred to as post-translational protein modifications (PTMs), is often responsible for the vast biodiversity found in nature. These modifications include acylation, methylation, phosphorylation, sulfation, farnesylation, ubiquitination, and glycosylation, among others, and play a pivotal role in important cellular processes including trafficking, differentiation, migration, and signaling.(2) Consequently, reproducing in a highly efficient and controlled way such natural modifications of proteins (by introducing natural PTMs) would provide an invaluable tool to study their precise function. Additionally, the possibility offered by the introduction and (bio)orthogonal modification of unnatural moieties/amino acids (usually improving the properties of natural PTMs during isolation, analysis, and processing)(3) makes site-selective modification of proteins a key tool for interrogating and intervening biological systems both in vitro and in vivo.(4)

Given the range of chemical modification methods available, it is now possible to decide which residue to target and which modification to attach in order to confer the desired property/function (affinity probes, fluorophores, reactive tags, etc.). For example, increasing the circulation half-life of a therapeutic protein may be achieved by the addition of polyethylene glycol (PEG). On the other hand, the use of a spectroscopic label to monitor biomolecule distribution in vivo enables the construction of highly selective imaging agents. Despite the vast progress in the field of bioconjugation chemistry, scientists still face many challenges, not only synthetically but also from a processing, manufacturing, safety, and stability perspective.(5) A number of methods have been developed and applied for the modification of particular proteins and therefore may not be applicable to any protein of interest. Thus, there remains a need for the development of complementary reactions for the site-selective chemical modification of proteins that are mild, efficient, and robust. Several reviews covering different aspects of the chemical synthesis of proteins, from general native chemical ligation strategies(6) and the modification of endogenous amino acids(7) to more specialized topics such as click modification protocols,(8) the introduction of particular PTMs including glycosylation,(9) PEGylation,(5b, 10) and polymerization of protein-based initiators,(11) and the challenging labeling of a specific protein of interest in a complex cellular mixture using the so-called “bioorthogonal” reactions,(12) have been published during the past decade.

While the later publications describe different protein syntheses/modifications in detail, the aim of the present review is not to be an exhaustive survey of all available bioconjugation methodologies but to discuss recent chemical strategies for the site-selective modification of proteins such as fast sulfur exchange or stable thioether formation, photo and metal-free cycloadditions, and other particularly challenging metal-mediated protocols. This review will be divided into two sections: transition metal-free and transition metal-mediated approaches. For clarity, we will use the following terminology throughout this manuscript: residue/amino acid/site-selective (or simply site-selective) reactions are those transformations that preferentially modify one amino acid residue over the others (e.g., cysteine versus lysine) and, thus, can be considered examples of chemoselective reactions; on the other hand transformations described as regioselective preferentially modify only one of a set of the same amino acid, in particular when more than one is present in the same molecule (e.g., solvent-exposed lysine versus internal lysine).

2 Transition Metal-Free Approaches

ARTICLE SECTIONS

Jump To

2.1 Classical Methods

The chemical modification of proteins aims to obtain new bioconjugates by performing chemical reactions on their original structures, maintaining both protein integrity and function. The ideal requirements for such reactions are those amenable with proteins such as functional group tolerance/compatibility, selectivity, water as a reaction media, at or near neutral pH and room temperature (or up to 40 °C), high reaction rates, low reactant concentrations, and nontoxic reagents, all to ensure high modification efficiencies that may avoid tedious and often inefficient purification/characterization protocols. Such a method would be a priori suitable for in vivo studies because it would not interfere with normal cell life. Classical protein bioconjugation methods have traditionally relied upon reactions at nucleophilic amino acids, particularly cysteine (Cys) or lysine (Lys) residues (Scheme 1).(13)

Cysteine easily undergoes disulfide exchange to form mixed disulfides(14) and also alkylation with suitable electrophiles that include α-halocarbonyls (e.g., iodoacetamide)(14) and Michael acceptors (e.g., maleimides or vinyl sulfones)(15) (Scheme 1d–f). The stability of some of the resulting conjugates, particularly those with a 1-S-3-carbonyl motif, may be compromised under certain conditions due to retro-Michael side-reactions and other thiol-promoted exchange processes,(16) yet this issue can be minimized by reducing the electron-withdrawing ketone to secondary alcohol under mild conditions in a second step.(17) Although the nucleophilicity of Lys may interfere with classical methods used for Cys modification, the low abundance of Cys in combination with fine-tuning the pH of the media or by modulating the residue’s pK_a with different steric and chemical environment enables a certain degree of site-selectivity. Lys modification is a popular protocol because of the availability of methods to preferentially modify primary amines (although often these methods also modify the N-terminus).(18) These protocols involve direct reaction with electrophilic reagents such as activated acids, vinyl sulfones, sulfonyl chlorides, iso(thio)cyanates, and squaric acids as well as reductive amination reactions with aldehydes (Scheme 1a–c). More sophisticated alkylation agents, such as cyclohexene sulfonamide derivatives, have recently been developed for the site-selective labeling of Lys in human serum albumin (HSA), although cross-reactivity with Cys may occur in other proteins.(19) Indeed, the modification of Lys is often the first of a subsequent modification step by a second bioorthogonal reaction (e.g., click chemistry). However, the recent needs of well-defined therapeutic proteins such as homogeneous glycoprotein vaccines(20) have promoted extensive work on protocols that enable access to pure constructs even when using such classical methods, which typically show a limited degree of site-selectivity and regioselectivity. Thus, a careful control of reaction conditions allows traditional, robust, and operationally simple albeit a priori nonselective Lys modification protocols to be used with a level of regioselectivity as recently demonstrated by Adamo and co-workers.(21) In this study, the authors have developed reproducible batch-to-batch Lys alkylations of CRM₁₉₇ after mapping their reactivity profile using semiquantitative LC-MS/MS as well as computational analyses. Similarly, Weil and co-workers reported a site- and regio-selective Lys modification protocol via kinetically controlled acylation by stepwise addition of substoichiometric amounts of an activated N-hydroxysuccinimide (NHS) ester under mild conditions.(22) Although this protocol enables the modification of a single Lys, the enhanced reactivity of this residue is determined by a number of factors including solvent accessibility and chemical environment of the surrounding residues; therefore, the regioselective acylation of a different Lys may be difficult. The rational introduction of a Lys in a highly solvent-exposed site may overcome this limitation. Other scarcely utilized nucleophilic residues in classical alkylation/acylation methods include histidine (His), which reacts preferentially over Lys in a cAb-An33 nanobody using vinyl sulfones as alkylating agents,(23) arginine (Arg) and the acidic moieties, aspartic (Asp), and glutamic (Glu) or the C-terminus, which have been used, for example, to modulate lipase activity.(24) More recently, diazo compounds also proved suitable for the reversible alkylation of protein carboxylic moieties.(25) Although most of these methods are nonselective, their reliability and robustness (usually generating amide bonds) make them the methods of choice for worldwide biotechnological applications such as immobilization protocols for enzyme-linked immunosorbent assays (ELISAs), microarrays, or polymer beads. Methionine (Met) alkylation has also been exploited for the modification of synthetic polypeptides.(26) The alkylation of thioether groups in Met-containing peptides enable the reversible (by adding several S-Nu) introduction of a broad range of functional and reactive groups to yield stable sulfonium derivatives including carbohydrate probes, alkenes, alkynes, azides, boronic acids, and PEG chains. Remarkably, this transformation is compatible with the deprotection of other functional groups and proceeds at low pH (in dimethylformamide (DMF), H₂O, or 0.2 M aqueous formic acid) unlike other thiol alkylations that require higher pH values. Other nonselective methods not covered in this review include the protein cross-linking due to generation of highly reactive species, such as carbenes, nitrenes, and radicals.(7)

2.2 Modern Methods for Targeting Natural Amino Acids

2.2.1 Lysine and N-Terminus

Despite the general use of nonselective protein modification methods, new chemical tools to access homogeneous proteins for in vitro and in vivo applications have been developed for the modification of natural Cys, Lys, and tyrosine (Tyr) residues. Selected examples of the next generation of Lys modifications are depicted in Scheme 2. A highly selective Lys modification protocol, based on the rapid 6π-aza-electrocyclization reaction, has been successfully developed by Tanaka and Fukase (Scheme 2a).(27) The efficiency of this procedure depends on the accessibility of the primary amino group; hence, excellent selectivities due to very rapid reaction kinetics toward solvent-accessible Lys (10–30 min at 24 °C) were observed when compared with internal and N-terminal amines (>5 h at 24 °C). Importantly, this protocol has been not only used for the asymmetric synthesis of pyridine/indole alkaloid-type natural products but also developed into a nondestructive Lys-labeling Kit named ‘Stella⁺’, which proved effective as a labeling strategy for biomolecules (e.g., by positron emission tomography (PET) or fluorescence) and living cells.

Another method for selective Lys modification involves the use of 2-imino-2-methoxyethyl reagents (IME) through the formation of an amidine linkage (Scheme 2b). In particular, 2-imino-2-methoxy-1-thioglycosides have been successfully used for the selective modification of an α-l-rhamnopyranosidase(28) and more recently for the glycosylation of RNase A leading to semisynthetic neoglycoconjugates with mannose mono- and disaccharides.(29) Gois and co-workers have also developed a strategy to reversibly modify both the ε-amino group of Lys and the N-terminal position, based on the formation of stable iminoboronates in aqueous media (20 mM NH₄OAc, pH 7.0) at room temperature (Scheme 2c).(30) This transformation proceeds via formation of a dative B–N linkage, and examples of peptides and proteins successfully modified using this protocol include somatostatin and model proteins such as lysozyme, cytochrome c, ribonuclease A, and myoglobin. The modification is stable over a period of 5 h but proved reversible upon the addition of fructose, dopamine, or glutathione, most likely by the disruption of the B–N bond. Although residue-selective, this method is nonregioselective since multiple Lys and N-terminal positions are modified. An application of this technology includes the introduction of a fluorescent motif into the 2-acetylbenzene boronic acid reagent that enabled the modification of not only lysozyme but also N-(2-aminoethyl) folic acid, leading to conjugates that are selectively uptaked by cancer cells that overexpress folic acid receptors.(31) Similarly to the arene diazonium bioconjugation with Tyr described in the following section, Carreira and co-workers have developed an amine-selective method using diazonium terephthalates that ensures the irreversibility of this transformation via formation of a stable triazin-4(3H)-one ring (Scheme 2d).(32) The amino acid selectivity and high rate of this reaction is demonstrated by labeling several small peptide models containing Tyr, primary OH, and CO₂H as “potentially reactive” nucleophilic moieties and myoglobin, which is indeed nonregioselectively labeled at Lys and N-terminal positions with up to six modifications.

Selective modification of N-terminal positions in the presence of a primary ε-amino group from Lys residues is anticipated to be a difficult task. However, an N-terminal modification protocol using ketenes has been recently developed by Wong, Che, and co-workers (Scheme 2e).(33) A series of different peptides and proteins including insulin, lysozyme, RNase A, and the therapeutic protein for cancer treatment BCArg were selectively N-terminally modified using an alkyne-functionalized ketene at moderate temperatures (room temperature or 37 °C) and pH 6.3–9.2, resulting in excellent selectivity (N-terminal amino/ε-amino up to >99:1). The authors rationalize this selectivity on the basis of the lower pK_a of the N-terminal position (∼8) versus that for the ε-amino group of Lys (∼10), which seems to favor the acylation of the N-terminal amino using ketenes. The local environment of the N-terminal position and its solvent accessible area may also play a role in the observed selectivity. Although not the focus of the present review, selective N-terminal protein modification can also be efficiently achieved through native chemical ligation (NCL) strategies(4) as well as with a flexible chemoenzymatic approach using simple aminoacyl and fatty acid transferase substrates.(34)

2.2.2 Tyrosine

Several nontransition metal-catalyzed strategies have emerged for the modification of the electron-rich side-chain of Tyr residues in proteins, in a chemoselective fashion (Scheme 3). Initially Francis and co-workers(35) and more recently Barbas and co-workers(36) have independently demonstrated that several diazonium salts bearing electron-withdrawing para substituents (NO₂, COCH₃, and CONH₂) react chemoselectively with Tyr ortho to the phenol group (Scheme 3a). Interestingly, the introduction of ketones, aldehydes, and more recently alkynes(37) as an additional bioorthogonal handle at the para position allows for a second modification round, for example, with fluorophore reagents. Alternatively, the azo bond can be further reduced and the corresponding aniline can be acylated with, for example, acrylamides, introducing additional reaction points. An interesting complementary variant that works with diazonium derivatives that are substituted with an electron-donating moiety (ArNHCOR with R = CH₃, PEG) employs a genetically encoded 2-naphthol analogue of Tyr (NpOH).(38) The coupling is rapid (∼2 h), is selective (NpOH reacts preferentially over Tyr), and requires mild conditions (0 °C and pH 7.0).

Francis and co-workers have also developed a three-component Mannich-type reaction with aldehydes and anilines for the modification of Tyr residues (Scheme 3b).(39) The high selectivity of this transformation is demonstrated by the successful modification of solvent-exposed Tyr such as those found in lysozyme, RNase A, and chymotrypsinogen A. Drawbacks of the method include the unreactivity of more buried Tyr residues (e.g., in horse heart myoglobin) and cross-reactivity with both exposed tryptophan (Trp) residues and reduced disulfides. Interestingly, while Cys residues do not interfere with this reaction, reduced disulfides form dithioacetals. This conjugation method has enabled the introduction of isoindoline-based nitroxide spin labels for electron paramagnetic resonance (EPR) in a small chloroplastic protein CP12, which possess a single tyrosine together with disulfide bonds and Trp residues that remain unmodified.(40) Other methods for Tyr modification include the reaction with preformed imines (Scheme 3c)(41) and also with azomaleimides(42) via an aqueous ene-type reaction that involves a concerted [1,5]-hydride shift from the phenol residue (Tyr) to the RN═NR moiety (Scheme 3d). Recent examples of the later Tyr selective modification approach include the preparation of well-defined glycoconjugate vaccines(43) and DNA–protein conjugates in model streptavidin and myoglobin proteins.(44) A potential drawback of this method is the instability of cyclic diazodicarboxamides via formation of isocyanates in water, which readily react with Lys residues leading to urea byproducts. Yet, the authors overcome this issue by simply using tris(hydroxymethyl)aminomethane (Tris) buffer that functions as an isocyanate scavenger, thus yielding only Tyr-labeled conjugates.(43a)

2.2.3 Cysteine

Unlike the nonselective methods for Cys modification described in the previous section, the development of more selective protocols has grown exponentially.(13) In particular, the recent work by Davis and co-workers based on a “tag-and-modify” approach(45) describes a series of complementary methods for the site-selective Cys modification (Scheme 4). The time line of this rational conjugation approach starts from the easy disulfide exchange reaction to form mixed disulfides as well as a conceptually similar reaction using diselenides (Scheme 4a–c)(46) that produces more stable SeS-linked conjugates; it continues by the transformation of potentially cleavable disulfide linkages to more stable thioethers by desulfurization of disulfides and finishes by developing complementary Cys-elimination methods that give access to dehydroalanine (Dha),(47) a useful Michael acceptor from which thioethers can be obtained directly upon conjugate addition of thiol nucleophiles (Scheme 4d). A recent example by Brik and co-workers exploits the formation of Dha for the preparation of diubiquitin activity probes.(48) Remarkably, these methods allowed not only the incorporation of most of the common PTM mimics such as S-glycosides, thiophosphates, and thioprenyl units in a rapid and selective way but also the creation of more sophisticated proteins by introducing ¹⁹F- and ¹⁸F-fluorosugars(49) as potential imaging labels, the preparation of PEGylated proteins(50) (e.g., recombinant human granulocyte colony-stimulating factor, rhG-CSF), and homogeneous glycoconjugate vaccine candidates(51) as well as synthetic histone mimetics.(52) Indeed, some of the corresponding glycoproteins are amenable to being enzymatically modified by endoglycosidases (Endo A), giving access to higher glycoprotein complexity without the need of any other round of chemical or genetic protein manipulations.(53) One limitation of the conjugate addition to Dha approach is the potential racemization at the modification site and consequent formation of d/l diastereoisomers. However, thioether PTM mimics of histones obtained by this method were found to be functional both in immunoblot and enzymatic analysis.(52) Chiral dehydroalanines have been proposed to achieve stereoselective sulfa-Michael additions.(54) However, this approach seems limited to simple amino acid models.

Site-selective modification strategies have received particularly attention for the attachment of potent cytotoxic drugs to recombinant antibodies engineered with Cys residues at predetermined sites. Most antibody–drug conjugates (ADCs)(5c) are built through conjugation of N-ethylmaleimide linkers that contain a cleavable site for drug release (e.g., valine–citruline dipeptide).(55) More recently, Neri and co-workers proposed and described two traceless strategies for the modification of antibody fragments where the linkage formed after conjugation between antibody fold and drug is the cleavable site for drug release. The first method (Scheme 5a) explores the reactivity of C-terminal cysteines in the site-selective formation of mixed disulfides and uses Ellman’s reagent for the preactivation of the Cys residue.(56) The second (Scheme 5b) targets N-terminal Cys residues and explores the reactivity of the sulfhydryl side-chain with aldehyde-containing drugs(57) or 2-cyanobenzothiazoles(58) (CBTs) to form thiazolidine-linked conjugates.

Other modern Cys modification methods are summarized in Schemes 6–8. These include both alkylation (polar reactions) and more sophisticated photochemical activation methods based on thiol–ene/yne chemistry (radical reactions). The work by Baker, Caddick, and co-workers (Scheme 6a) relies on tunable bromo- and dibromomaleimides for multifunctional bioconjugation by either reversible or permanent Cys alkylation both in vitro(59) and in mammalian cells.(60) Aryloxymaleimides are also used as the next generation of tunable maleimides with attenuated reactivity enabling Cys modification strategies, disulfide bridging, and the dual functionalization of disulfide bonds.(61) While the thioether succinimide motifs that result from conjugate addition of the sulfhydryl group side-chain of Cys to maleimide readily undergo retro-Michael addition with biological thiols (e.g., Cys34 of HSA, the major constituent of plasma),(16) stable conjugates may be obtained using electron-withdrawing maleimides that are rapidly hydrolyzed to their ring-opened counterparts to ensure in vivo stability.(62) Bromo- and dibromopyridazinediones have also been used for the reversible modification of proteins at Cys and disulfides with four potential points of chemical attachment (Scheme 6b).(63) While this conjugation is reversible by a thiol exchange mechanism, the use of a tris(2-carboxyethyl)phosphine (TCEP)-based para-azidobenzyl temporary protecting group (R²) readily transforms these reversible reagents into irreversible conjugates.(64) A conceptually similar alkylation strategy (Scheme 6c)(65) revealed that bis-alkylation of the Cys residue (S147C) of a “superfolder” green fluorescent protein (GFP) with the 2,5-dibromohexanediamide developed by Davis and co-workers enables a two-step modification protocol by first creating an unexpectedly stable cyclic sulfonium intermediate that is subsequently opened with thiol, selenium, and nitrogen nucleophiles with good conversions (up to >95%) and mild conditions (21–37 °C). Analogously, the preparation of a double Cys mutant of the superfolder GFP by rational positioning of two cysteines with different local chemical environments and reactivities allows precise control of the regioselective formation of both Dha and cyclic sulfonium intermediate on the surface of the same protein. Subsequent ring opening of the cyclic ion with sodium azide generates two orthogonal handles (Dha and N₃) that enable dual labeling upon reaction with thiol and alkyne probes, respectively.(66)

Cys can also add to electron-deficient alkynoic amides/esters and alkynones, leading to the corresponding vinyl sulfides in aqueous media (Scheme 6d).(67) This reaction proved to be fast (terminal alkynone ≫ internal alkynone = alkynoic ester > alkynoic amide), compatible with other nucleophilic amino acid residues (Ser, His, Met, Lys, and Tyr with only limited cross-reactivity with N-terminal Ala and certain alkynones) and reversible in nature; therefore, Cys can be recovered by addition of an external thiol via a base-induced thiolate exchange. A recent application of this technology involves the preparation of phosphorescent proteins by introducing luminescent cyclometalated iridium(III) complexes as potential bioimaging agents.(68) Other electron-deficient triple bonds that have been employed for chemoselective Cys alkylations include 3-arylpropiolonitriles (Scheme 6e).(69) The reaction is fast and provides hydrolytically stable conjugates that may be useful in Cys-selective bioconjugation strategies. The authors attribute this stability to the presence of an aryl moiety that reduces the electronic density of the alkene unit by delocalization on the aromatic ring.

Boons, Popik, and co-workers have demonstrated the selective and reversible photochemical derivatization of cysteine residues on proteins using 3-(hydroxymethyl)-2-naphthol derivatives (NQMPs) (Scheme 7a).(70) The formation of transient Michael acceptors upon irradiation of NQMPs at 350 nm enables the rapid attack of Cys and the formation of hydrolytically stable thioether linkages as demonstrated by the conjugation of several probes (PEG, dyes, carbohydrates, and other alkynes, azides, and biotin-labeled units) into model bovine serum albumin (BSA). Interestingly, this transformation is reversible upon irradiation of dilute solutions or in the presence of vinyl ethers (see also Scheme 15i).

Xian and co-workers first reported the Julia–Kocienski-like reagent methylsulfonyl benzothiazole (MSBT) as a selective protein thiol blocking agent in glyceraldehyde 3-phosphate dehydrogenase (GAPDH),(71) and later Barbas and co-workers expanded this methodology as a rapid thiol-selective protein modification strategy in a recombinant HSA and a fusion maltose-binding-HA peptide protein (MBP-C-HA), generating fluorophore and PEGylated conjugates superior in stability to maleimide-conjugated proteins in human plasma (Scheme 7b).(72) Indeed, this novel protocol also enabled the site-selective labeling of engineered Cys but also selenocysteine (Sec) residues of antibody conjugates, successfully improving their stability in human plasma.(73)

Recently, Abbas, Xing, and Loh have employed allenamides as privileged orthogonal handles for Cys-selective protein modification in aqueous media (Scheme 7c).(74) The Michael-type addition enables the fast formation of a stable and irreversible vinyl sulfide conjugate, and its utility was demonstrated for the selective labeling at Cys (or disulfides after treatment with dithiothreitol (DTT)) of small peptides (e.g., glutathione (GSH)) as well as on BSA and the antibiotic-resistant bacterial enzyme TEM 1 β-lactamase (Bla).

Most of the site-selective methods described above rely on the unique reactivity of Cys in comparison to other nucleophilic residues. However, it is rather challenging when the introduction of two different modifications in two Cys units is required. To achieve this goal, the identification of Cys environments that render sufficient differences in the reactivity of the sulfhydryl side-chain of Cys may allow dual-selective Cys modifications. It is well-known that solvent accessibility and local charge strongly modulates Cys reactivity. In one example, the introduction of charged amino acids proximal to a Cys decreases the pK_a of the sulfhydryl moiety (by electrostatic interactions) and therefore accelerates its reaction with electrophiles, whereas the opposite trend is observed with negatively charged residues.(75) In another example, the protonation state of the N in vinyl-substituted pyridine derivatives (Michael-like acceptors) in combination with the local environment of the Cys also led to differences in reactivity toward these vinyl tags.(76) Additionally, cysteine mutations at specific positions in designed ankyrin repeat proteins (DARPins) allow the sequential alkylation of the strongest nucleophilic Cys with a weak thiol-reactive reagent (bromoacetamide) followed by treatment with a more reactive maleimide that reacts with the less nucleophilic Cys.(77) A conceptually similar approach exploits the preferential succinimide hydrolysis occurring in positively charged environments, which leads to a more stable conjugate and prevents detrimental maleimide exchange reactions with plasma thiols. This has been utilized for the modulation of the in vivo stability and therapeutic activity of antibody–drug conjugates (ADCs).(78)

Alternatively, the formation of stable thioethers can also be efficiently achieved using the emerging thiol–ene(45, 79) and thiol–yne(80) couplings with native Cys proteins where radical species are typically generated using either radical initiators or light (Scheme 8). While thiol–ene coupling enables the introduction of a single molecule, the complementary use of alkynes allows for double functionalization and, thus, the incorporation of different modifications such as glycoconjugates, peptides, and fluorescent probes. The transformation proceeds by a first radical addition to form a stable vinyl sulfide moiety that undergoes a second radical addition with a different thiol, to finally obtain a 1,2-modified thioether under mild conditions. Despite advances of both thiol–ene/yne reactions for site-selective chemical protein modification of native proteins, the implementation of these methods is limited because the formation of thiyl radicals may damage the protein structure.

Although nonselective Cys alkylation is often expected when using electrophilic reagents, some degree of site-selectivity is achieved by fine-tuning the reaction conditions (without any additional mutation) and particularly by using a Cys-rich Cys-(X)_m-Cys-(X)_n-Cys (m and n = 3–6) motif with electrophilic trihalides (Scheme 9a). Heinis and co-workers have successfully exploited this strategy for generating cyclic peptide regions by alkylation of Cys side-chains with the trivalent tris(bromomethyl)benzene (TBMB) under mild conditions in aqueous media, leading to a general protocol for attaching and evaluating the proteolytic stability, half-life, and other important biological properties in phages, antibodies, and peptide fragments.(81) Crown ether-like supramolecular libraries(82) and phage selection of photoswitchable peptides(83) are also accessible using this technology. Similarly, Pentelute and co-workers have reported the preparation of hybrid macrocyclic peptide libraries via a chemoselective S_NAr with perfluorinated benzene derivatives, which allow the fine-tuning of the dimensions and chemical composition of the peptide macrocycles (Scheme 9b).(84)

The genetic incorporation of Cys-rich peptide sequences has also been exploited for the chemical labeling of proteins, for example, using a tetracycline fluorophore with biarsenical-functionalized fluorescent dyes, one of the first examples of a bioorthogonal approach in Chemical Biology.(85) For more information on this as well as other peptide motifs that can be modified through chelation with transition metals (e.g., Ni(II)-His-tag pair)(86) via ionic interactions or by enzymatic reactions,(87) the reader is directed to these general reviews.(12a-12h, 88) Alternative site-selective protein modification methods, typically exploiting those nucleophilic natural amino acid residues (Cys, Lys, Glu, Asp, etc.) employed in nonselective protocols, have been also reported in conjugation protocols based on proximity-induced reactions and recognition or ligand-directed strategies using a wide range of conjugation chemistries including alkylation with electrophilic handles(89) (e.g., α-chloroacetamides, tosylates, DMAP/imidazole-activated acyl units, genetically encoded vinyl sulfonamides, etc.), disulfide formation,(90) and radical trapping via local single-electron transfer catalysis.(91) These robust transformations provide a certain degree of selectivity in contrast to the nonrecognition, old-fashioned methods.

2.2.4 Disulfides

The modification of native disulfide bonds through bis-alkylation protocols has attracted growing interest in recent years since the rise of novel therapeutic proteins in the global biotechnology market has stimulated the development of new methods for improving the properties and safety of these protein-based pharmaceuticals (Scheme 10). Among these technologies, the work by Shaunak and co-workers was found to be particularly useful (Scheme 10a). Disulfide modification allows the site-selective conjugation of poly(ethylene glycol) (PEG) or other polymers to proteins from which optimal pharmacokinetics are achieved, hence ensuring protein purity, maintenance of tertiary structure, and stability.(92) Mechanistically, the conjugation is conducted by a sequential, iterative bis-alkylation using α,β-unsaturated-β′-monosulfone functionalized PEG reagents, leading to a stable thioether bridge. This protocol efficiently modifies a broad range of peptides, proteins, enzymes, and antibody fragments that can be site-selectively PEGylated or conjugated to potent cytotoxic payloads using a native and solvent-accessible disulfide moiety.(93) This methodology may also be applied to proteins bearing a polyhistidine tag (His-tag) through the same bis-alkylation principle of reactivity.(94)

Similarly, Haddleton, Caddick, and co-workers employed dibromo-(95) and dithiophenolmaleimides(96) and Baker and co-workers used aryloxymaleimides(61) as bis-alkylating reagents for the in situ bridging of disulfides allowing the incorporation of PEG chains in a very efficient manner at pH 6.2 (Scheme 10b). This reaction benefits from the rapid reaction kinetics, high efficiency, and reduced purification due to the use of equimolar equivalents of both peptide and polymer. Importantly, while this thiomaleamic acid linker is stable under physiological conditions, it is readily cleaved at lysosomal pH (around 4.5) and temperature (37 °C) enabling the preparation of homogeneous ADCs (trastuzumab Fab fragment) at disulfide sites and their subsequent controlled payload release.(97) Homogenous bispecific antibodies (able to bind two different antigens) have been also built using a bis-dibromomaleimide cross-linker.(98)

2.3 Modern Methods for Targeting Unnatural Amino Acids

2.3.1 Carbonyl Handles

The incorporation of unnatural amino acids (UAAs) combined with chemical protein synthesis enables access to chemically modified biomolecules that are difficult to obtain using standard molecular biology methods. Often the unnatural amino acid (e.g., alkene/alkyne groups, azido groups, or carbonyl groups) serves as a privileged reaction handle that can undergo further bioorthogonal modifications.(12) Several strategies, both chemical and genetic, have been developed for the incorporation of carbonyl functionalities into proteins that enable subsequent chemical modification (Scheme 11).

Early strategies used genetically encoded aldehydes and ketones that can be selectively labeled with hydrazides and aminooxy groups to form hydrazones and oximes, respectively (Scheme 11a and b) as well as Trp derivatives (Scheme 11d). Alternative (chemo)enzymatic strategies use two-step procedures involving, first, a chemical oxidation with (i) sodium periodate (including those methods based on oxidation of carbohydrate moieties),(99) (ii) a site-selective transamination reaction(100) with pyridoxal 5′-phosphate or related reagents (Rapoport’s salt), or (iii) an enzymatic tagging with formylglycine-generating enzymes (FGEs)(101) to efficiently install an aldehyde (or ketone) handle that can be modified with a second, carbonyl-selective reaction.(102) Among these, relevant examples include the well-known oxime (Scheme 11a)(103) and hydrazide (Scheme 11b)(104) ligations together with a related reaction with 2-amino benzamidoxime (ABAO) derivatives (Scheme 11c),(105) the Pictet–Spengler ligation (Scheme 11e),(106) which is more rapid than its parent version (Scheme 11d), and, more recently, the so-called hydrazino-Pictet–Spengler (HIPS) ligation (Scheme 11e).(107) The HIPS ligation is fast (k₂ = 4.17 ± 0.19 M^–1 s^–1); proceeds at near neutral pH 6, allowing the direct labeling of proteins under mild conditions; and, importantly, yields stable conjugates. Moreover, the HIPS ligation has been recently employed for the preparation of ADCs by site-selective conjugation at different sites, hence with variable in vivo efficacy and pharmacokinetics.(108) Aside from the aforementioned reactions, the aldehyde moiety can also be used for selective protein modification, generating stable C–C bonds by the Wittig reaction.(109) Moreover, the biocompatibility of such a reaction enables the application of stabilized phosphorus ylides in live cell affinity isolation and fluorescence labeling of proteins (Scheme 11f).(110)

2.3.2 Alkynes, Alkenes, and Dipole Handles

The development of complementary chemical, enzymatic, and genetic methods for introducing and using azide moieties(111) (a privileged 1,3-dipole handle) as bioorthogonal reporter groups has made this reactive functional group a routine choice for protein modification strategies. Schemes 12 and 13 summarize the bioorthogonal reactions developed for the modification of proteins equipped with azides and other dipoles. Early methods employed azide-functionalized proteins together with the classic Staudinger reaction to install amide-linked modifications (Scheme 12a).(12a-12h) While in the original strategy the phosphine oxide generated remains incorporated into the protein, the “traceless” version (Scheme 12b)(112) overcomes this limitation, hence improving the overall transformation, especially in applications where a minimalist amide bond is required. Recent variants developed by Hackenberger and co-workers (Scheme 12c) expanded this type of chemistry to other phosphorus moieties, developing the corresponding Staudinger-phosphite(113) and Staudinger-phosphonite ligation protocols,(114) leading to phosphoramidate or phosphonamidate linkages, respectively. These linkages mimic natural occurring phosphoric esters and have the potential of introducing either one or two molecular probes into the same protein as exemplified by the successful PEGylation of Calmodulin.

Alternatively, azide handles also participate in [3 + 2] cycloadditions with strained alkynes (Scheme 12d), in a reaction usually referred to as a copper-free azide–alkyne “click” reaction,(115) which represents a significant improvement of the former uncatalyzed Huisgen reaction and other metal-catalyzed versions with Cu(I) and Ru(II) (Schemes 19a–c and 20a and b) . The strain-promoted alkyne–azide cycloaddition (SPAAC) represents a powerful tool not only for protein and antibody labeling (for example, for the construction of homogeneous ADCs)(116) but also for other applications such as antibody-free Western Blot analysis.(117) This is mainly due to the fact that no additional reagents or toxic metals that may damage proteins are required; the reaction proceeds with a rapid rate (k₂ up to 0.96 M^–1 s^–1 when the appropriate cyclooctyne is employed). Indeed, the success of this reaction is related to the fine-tuning of reactivity/selectivity ratio, taking into account important parameters such as lipophilicity (nonselective binding) and cross-reactivity with the biological thiols (leading to alkenyl sulfides).(80, 118) Moreover, other derivatives present in the media in small quantities such as sulfenic acids (RSOH), which are formed by the reaction of reactive oxygen species (ROS) with protein thiols, rapidly cross-react with strained cyclooctynes to afford alkenyl sulfoxides.(119) This reaction may become a valuable tool for dissecting the roles of protein sulfenic acids in vitro and in vivo.

Other 1,3-dipoles such as nitrones and nitrile oxides have gained popularity during the past few years as handles for bioorthogonal strain-promoted cycloadditions (Scheme 13). van Delft, Boons, and co-workers developed the so-called bioorthogonal strain-promoted alkyne–nitrone cycloaddition (SPANC) following a one-pot, three-step protocol consisting of the chemical introduction of a terminal aldehyde handle by serine oxidation with periodate, its subsequent transformation into a nitrone using N-methylhydroxylamine, and finally reaction with the corresponding cyclooctyne (Scheme 13a).(120) This efficient site-selective modification protocol is fast (typically 10 times faster than SPAAC), and its robustness has been demonstrated not only for the modification of the chemokine interleukin-8 (IL-8) but also in the recent site-selective conjugation of ScFvs antibodies to nanoparticles.(121) A valuable variant of the SPAAC reaction with nitrones employs protein equipped with nitrile oxides (Scheme 13b) as reactive handles to explore an operationally similar (oxime formation–oxidation–cycloaddition) strain-promoted alkyne–nitrile oxide cycloaddition (SPANOC).(122) Recently, a fast copper-free strain-promoted sydnone–alkyne cycloaddition (SPSAC) between 4-halosydnones and bicyclo-[6.1.0]-nonyne has been reported (Scheme 13c).(123) Structural motifs increasing the partial positive charge at the N-3 atom of the sydnone ring (N-aryl moieties bearing strong electron-withdrawing groups) proved beneficial to the reaction. Among those, 4-Cl N-aryl sydnone was the best performer, with model bicyclo-[6.1.0]-nonyne showing reaction rates of up to k₂ = 1.593 ± 0.034 M^–1 s^–1, and was subsequently utilized for the modification of a sydnone-functionalized BSA with a fluorescent cyclooctyne derivative.

Isonitriles also react via [4 + 1] cycloaddition with tetrazines in aqueous media as demonstrated by the introduction of a fluorophore into the tertiary isonitrile-labeled C2A domain of synaptotagmin-I (Scheme 13d).(124) Hydrolysis of the isonitrile moiety to the corresponding amine can be minimized using tertiary analogues.

Alkynes and alkenes can also be incorporated into proteins and used in a wide range of bioorthogonal reactions (Schemes 14 and 15). Simple alkynes such as alkynyl–pyrrolysine analogues are incorporated and modified without any metal catalyst using a site-selective thiol–yne coupling (Scheme 14a).(125) Alternatively, protein encoding with cyclooctynes (Scheme 14b and c) using either chemical(126) or genetic(127) methods has been exploited in metal-free protocols with azides or tetrazine reagents as shown in previous sections. An interesting application includes the postfunctionalization of virus particles via azide–alkyne click chemistry (including the comparison with the Cu(I) variant) demonstrating the preservation of capsid integrity and its self-assembly properties.(128)

More recently, Wallace and Chin have reported a strain-promoted sydnone 1,3-dipole bicyclo-[6.1.0]-nonyne cycloaddition,(129) demonstrating that this metal-free transformation is biocompatible and proceeds in aqueous buffer at physiological temperature with complete conversion/selectivity albeit with moderate rates (0.054 M^–1 s^–1) (Scheme 14d).

While oxanorbornadienes react with azides (Scheme 15a) and norbornenes equipped with electron-deficient sulfonyl azides (Scheme 15b),(130) other alkenes such as strained trans-cyclooctenes, cyclopropenes, norbornenes, acrylamides, or simple vinyl/allyl alcohols have received considerable attention because of their fast reaction rates in inverse-demand Diels–Alder reactions with tetrazines(131) and 1,3-dipolar cycloadditions with in situ chemical or photogenerated nitrile–imine dipoles (Scheme 15c–g).(131c, 132) Of particular relevance is the selective inverse-electron-demand Diels–Alder reaction of tetrazines with isomeric 1,3-disubstituted cyclopropenes, as well as the 1,3-dipolar cycloaddition of nitrile imines (generated by “photoclick” reaction from tetrazole) with 3,3-disubstituted cyclopropenes(133) or spiro[2.3]hex-1-enes (with an impressive k₂ up to 34 000 M^–1 s^–1).(134) This unique, orthogonal reactivity resulting from rational positioning of a single methyl group into a cyclopropene moiety will be beneficial in dual labeling strategies both in vitro and in vivo. The reverse protocol, using tetrazine-modified proteins instead, is also an alternative for such labeling methods.(109, 135) For a more in depth description of the reaction kinetics as well as other particular aspects of these transformations, the reader is directed to recent and comprehensive reviews.(12a-12h) Indeed, these highly efficient transformations enable double labeling strategies such as the modification of several pairs of sites in Calmodulin with fluorophores for determining protein structure and dynamics.(136) Acyclic alkenes such as homoallylglycine (Hag),(51, 137) alkenyl–pyrrolysine analogues, and acrylamides also react in a site-selective manner with thiol probes under radical conditions by a thiol–ene ligation (Scheme 15h).(125) Other chemistries have also been explored with a dienophile(vinyl sulfide) functionalized protein and o-quinolinone quinone methide as diene(138) or with maleimide-tagged proteins with 5-alkoxyoxazoles (via Kondrat’eva irreversible cycloaddition)(139) in hetero-Diels–Alder reactions (Schemes 15i and 16b) as well as with diene-functionalized proteins in classical Diels–Alder reactions with maleimides (Scheme 16a).(8) Importantly, and unlike most of the reversible Diels–Alder-based reactions, the Kondrat’eva hetero-Diels–Alder is an irreversible ligation that has recently been added to the click chemistry toolkit. This reaction occurs under slightly acidic conditions (0.1 M NaOAc buffer, pH 5.0 at 37 °C) between 5-alkoxyoxazoles and maleimides, affording stable pyridine moieties as demonstrated by the labeling of BSA–maleimide with a fluorescent dye.(139)

N-Acylazetine (the N-analogue of cyclobutene) is another dienophile that has not been used yet for protein modification but holds a great potential.(140) This achiral and minimalistic non-native functional group has been successfully employed in the two-step activity-based protein profiling of catalytically active proteasome subunits using tetrazine-based bioorthogonal chemistry (k₂ = 0.39 ± 0.1 M^–1 s^–1).

3 Transition Metal-Mediated Approaches

ARTICLE SECTIONS

Jump To

Significant advances in both genetic and synthetic methods over the past few years have allowed the use of nonbiological metal-mediated reactions for protein modification protocols.(141) Some of the limitations that traditionally faced organometallic transformations such as the use of anhydrous solvents and catalyst poisoning (typically associated with the reaction of the catalyst with soft, nucleophilic residues) have been progressively solved, and a range of novel reactions have emerged, expanding the toolkit of selective bioorthogonal transformations.(1, 4, 142) These new protocols should fulfill not only the “on protein” reaction conditions—aqueous media, high efficiency, and chemoselectivity at or near room temperature and over a narrow pH range—but also those of an efficient, environmentally benign catalytic system: moisture and air-stable ligands or ligandless systems that enable mild, fast, and economic processes. The most significant contributions and challenges associated with metal-mediated protein modification protocols targeting both natural or unnatural amino acid residues will be highlighted in the following sections.

3.1 Methods for Targeting Natural Amino Acids

3.1.1 Lysine and Tyrosine with Iridium and Palladium Complexes

Early metal-mediated protein modification methods focused on the modification of nucleophilic natural residues such as Lys and Tyr (Scheme 17). Reductive alkylation of surface-exposed Lys residues using a Cp*–Ir bipyridyl complex enabled the condensation of aliphatic and aromatic aldehydes.(143) The formed imine is subsequently reduced by an active Ir–hydride species, which is generated in situ from sodium formate at pH 7.4 and room temperature (Scheme 17a). However, low selectivity is observed because the protein N-terminus is also modified. Alternatively, Francis and co-workers explored the palladium-catalyzed Tsuji–Trost modification of Tyr (Scheme 17b). The authors reported the use of π-allylpalladium complexes, which are generated from allyl acetates/carbamates and Pd(OAc)₂/triphenylphosphine tris(sulfonate) (TPPTS) as a catalytic system, for selective Tyr O-alkylation with a rhodamine dye and lipophilic moieties.(144) Moderate conversion (50–65%) to a singly solvent-exposed alkylated product was obtained although a small amount of doubly alkylated product was also observed. Examples of this Pd-catalyzed Tyr-selective strategy include the selective introduction of different fluorophores into bovine erythrocyte Cu/Zn superoxide dismutase (SOD)(145) and HSA.(146)

Other metal-mediated modifications of Tyr, Trp, N-terminal amino acids (e.g., proline), and other unnatural residues involving oxidative couplings with Ni(II), Ce(IV), or Fe(III) are not covered in the present work because they simply act as oxidants in these transformations, yet they have also been explored for chemical protein modification.(1, 142, 147)

3.1.2 Natural Residues with Rhodium and Gold Complexes

Pioneering work by Francis and co-workers shed light into the use of rhodium carbenoids for protein modification targeting Trp residues, yielding mixtures of N-1 and C-1 regioisomers (Scheme 18a).(148) However, the general applicability of this transformation is limited due to the low pH <3 required. Improved reaction conditions requiring only a slightly acidic media (pH 6) were reported, but the conversions were only moderate.(149) Solvent-accessible Cys residues also react with rhodium carbenoids via S–H insertion of a metallocarbene intermediate as exemplified by the modification of the PDZ domain of the cystic fibrosis transmembrane conductance regulator-associated ligand (CALP) (Scheme 18c).(150) Alternatively, peptide-based molecular recognition strategies (Scheme 18b) with metallopeptides have also been used to site-selectively modify proteins by targeting proteinogenic residues including Phe, Tyr, Asn, Gln, Lys, and His, among others that were unreactive under standard conditions with simple Rh₂(OAc)₄ catalysts.(45, 151)

Wong, Che, and co-workers have described the gold-mediated selective cysteine modification of peptides and proteins using allenes, which represents the first utilization of gold complexes for protein modification (Scheme 18d).(152) The reaction is formally an oxidative allene–thiol coupling in aqueous media at room temperature using AuCl/AgOTf as a catalytic system. Although this protocol has been successfully employed in peptides (up to 97% conv.), the modification of RNase A resulted in reduced conversion and regioselectivity (24% single modification together with 9% of the doubly modified protein).

3.2 Methods for Targeting Unnatural Amino Acids

3.2.1 Azides, Sydnones, Alkynes, and Alkenes

Recent advances in the incorporation of unnatural amino acids into proteins(153) have stimulated the development of novel methodologies for their modification as well as the recycling of well-known and established protocols. As such, unnatural reactive handles provide a privileged chemical point from which metal-mediated strategies, usually developed earlier, may efficiently work by reassigning the reaction conditions for such transformations using aqueous, mild, and atmospheric-tolerable catalytic systems. In this section, we describe recent developments that have allowed these protocols to become attractive tools for selective chemical protein modification. Schemes 19–21 illustrate a range of methods used for the transition metal-mediated modification of azides, sydnones, alkynes, and alkenes.

Early examples include the modified Huisgen cycloaddition also referred to as Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC) or “click reaction”, which represents one of the most important bioconjugation methods for protein modification reported to date (Schemes 19a and 20a).(154) Catalytic amounts of Cu(I) are sufficient to promote a mild chemoselective [3 + 2] cycloaddition in aqueous media that produces hydrolytically stable and amide isosteric 1,4-disubstituted triazole rings. This method has been used to access and study a wide range of important PTMs,(4, 8) including cases of dual, orthogonal PTMs,(155) or in site-specific immobilization protocols.(156) In addition, the introduction of ¹⁹F- and radiolabeled ¹⁸F-glycosyl probes on an Hpg-functionalized globular protein SsβG (β-galactosidase) and also on a multivalent and self-assembled virus-like bacteriophage particle Qβ (with 180 F-glycosyl units incorporated) was achieved under CuAAC conditions. This approach allows the design of homogeneous glycoprotein probes for structural dynamics (e.g., ¹⁹F–NMR) and imaging (e.g., ¹⁸F-positron emission tomography (PET)) purposes.(157) However, and despite the enormous success of this protocol and the progress made on the development of ligands and complexes (e.g., N-heterocyclic carbene–Cu catalysts)(158) that stabilize and maintain the active catalytic Cu(I) species, there are still some limitations including protein damage and associated toxicity. This is likely due to the generation of ROS, which have progressively favored the utilization of more friendly Cu-free protocols (Schemes 12 and 13).(159) Using a high-throughput immunoassay screening, Taran and co-workers discovered sydnone 1,3-dipoles as an alternative handle that also reacts with Cu(I) in chemoselective and biocompatible fashion in the so-called Cu-catalyzed sydnone–alkyne cycloaddition (CuSAC) (Scheme 19b),(160) similar to the metal-free variant depicted in Scheme 14d. This transformation was demonstrated with a sydnone-functionalized BSA that was reacted (ca. 75% conv.) with a dansyl-labeled alkyne using CuSO₄/Na ascorbate/ligand system in PBS buffer (pH 8.0) at 37 °C. This transformation, however, does not proceed with N-alkyl sydnones. Ru(II) has recently emerged as an alternative metal able to catalyze [3 + 2] cycloadditions of both terminal and internal alkynes with azides (RuAAC), leading to otherwise elusive 1,5-disubstituted triazoles (Schemes 19c and 20b). Thus, RuAAC has been used as a way of introducing cis-peptide bond surrogates in pancreatic ribonuclease (RNase A).(161)

Another transformation that takes advantage of an alkyne handle is the palladium-catalyzed Sonogashira cross-coupling in aqueous media (Scheme 20c and d). Palladium catalyzed cross-coupling reactions in aqueous media(162) have been widely studied and developed over the last 30 years on small-molecule models. As such, reactions with peptide substrates are not covered in the present section, which highlights recent achievements using functionalized proteins bearing suitable unnatural residues. Thus, copper-free Sonogashira cross-coupling at homopropargylglycine (Hpg) is a useful method for C–C bond formation between alkynes (Csp) and aryl halides (Csp²) enabling the efficient attachment of aromatic groups, including fluorophores and PEG chain motifs to ubiquitin,(163) ubiquitin-fused peptides selected from phage display,(164) and a model dihydrofolate reductase (eDHFR) from E. coli, which was designed with an N-terminal 13 amino acid lipoic acid acceptor peptide (LAP) sequence.(165) This approach has also been successfully used for the labeling of proteins in bacterial cells (E. coli)(163) and in the surface of mammalian cells.(166) The success of this transformation in live cells is dependent on the use of water-soluble 2-amino-4,6-dihydroxypyrimidine (ADHP) ligands (Scheme 20c). Recently, an improved copper-free Sonogashira cross-coupling at pyrrolysine (Pyl)-based systems has been reported by Chen and co-workers (Scheme 20d).(167) The authors identified Pd(NO₃)₂ as an effective nontoxic (with diminished membrane damage potential) catalyst that works efficiently at room temperature (25 °C) in live E. coli and Shigella cells. This method was applied for the intracellular labeling and visualization of type-III Secretion (T3S) toxin-OspF.(167) The authors suggest the generation of Pd(0) nanoparticles from the Pd(II) source and an electron donor–sodium ascorbate in the reaction mechanism of this process. The use of similar catalysts enabled Pd-triggered deprotection and subsequent activation of N^ε-propargyloxycarbonyl-l-lysine and N^ε-allyloxycarbonyl-l-lysine containing proteins in cells.(168) Finally, another site-selective metal-catalyzed cross-coupling at Hpg-functionalized ubiquitin exploits water-stable palladacycles to form styrene adducts with fluorescent and PEG modifications in moderate to high yields in PBS buffer at 37 °C (Scheme 20e).(169)

The Nobel-winning olefin cross-metathesis (CM) reaction represents another well-known C–C bond-forming reaction that has recently been added to the pool of bioorthogonal transformations for chemical protein modification (Scheme 21).(170) Davis and co-workers successfully demonstrated the first cross-metathesis couplings with an S-allylcysteine (Sac)-functionalized protein.(171) In this case, the first step involves the chemoselective installation of a Sac handle that may be achieved using complementary methods.(172) The second step is an aqueous cross-metathesis reaction catalyzed by air-stable Hoveyda–Grubbs second-generation catalyst, which is enhanced by the presence of S-allyl moieties and suggested to proceed via a chalcogen-relayed mechanism (Scheme 21a). This behavior is also known as allylic chalcogen effect(173) and rationalizes the reactivity enhancement of allylic chalogenides by a chelation mechanism that can be exploited to efficiently attach a wide variety of alkenes. Important issues of this transformation include (i) the need to use 30% tBuOH as a solvent system to reduce the poor water solubility of conventional Ru catalysts, (ii) the use of MgCl₂ as a mild Lewis acid to prevent nonproductive chelation of other nucleophilic moieties, and, finally, (iii) the fact that reaction completion was only observed with allyl alcohol. This observation points out steric hindrance as a possible limitation of this approach. This limitation was addressed by the use of a linker-extended version together with a more reactive Se-allylselenocysteine (Seac) handle, which allowed successful reaction with previously unreactive metathesis partners (Scheme 21b).(171) Next, the direct installation of a rare C–Se bond on a protein surface via biomimetic addition of allylselenoate to Dha-functionalized proteins suppressed the need for the linker and enabled cross-metathesis to proceed with alkene counterparts (allyl GlcNAc and N-allyl acetamide) that were previously not possible with the corresponding Sac analogue.(174) Reaction kinetics revealed rate constants (k₂ = 0.3 M^–1 s^–1) comparable or superior to many current bioorthogonal reactions. Interestingly, this transformation is reversible upon treatment with H₂O₂ via Cope-type selenoxide elimination, which was exploited in a synthetic write (CM)–read (antibody)–erase (elimination)–rewrite (CM)–read (antibody) cycle at the epigenetic site 9 (N-acetyl Lys derivative) of histone H3. Moreover, using the same catalytic system, Schultz and co-workers performed a related ring-closing reaction at genetically encoded alkenes in yeast.(175)

Another bioorthogonal Pd-mediated transformation has been recently added to the alkene modifications toolbox. Dekker and co-workers employed a single Cys mutant of enzyme 4-oxalocrotonate tautomerase (4-OT), which was alkylated with several maleimide-containing alkenes, to develop an oxidative Heck reaction for mild bioconjugation in vitro (Scheme 21c).(176) This strategy enabled the chemoselective introduction of several boronic acids with excellent conversions into a single alkene-functionalized protein using a base-free catalytic system with Pd(OAc)₂ and the bis-imine of acenaphthenequinone and mesitylamine (BIAN) as a ligand in the presence of complex protein mixtures and importantly under aerobic conditions. Alkene tolerance was remarkable because not only terminal but also cis ≫ trans internal alkenes, which represent an interesting cis-selective alkene modification protocol, were modified, leading to mixtures of linear/branched final products as demonstrated in small-molecule models.

Alternative couplings exploiting allylic disulfides have also been utilized but only in peptide models. These include the desulfurization of allylic disulfides followed by a silver-mediated allylic rearrangement(177) and the Kirmse–Doyle reaction, which consists of the generation of a sulfur ylide upon attack of a rhodium carbenoid and subsequent rearrangement.(178)

3.2.2 Aryl Halides and Boronates

Aside from the aforementioned copper-free palladium-catalyzed Sonogashira cross-couplings at proteins equipped with alkyne handles (Scheme 20c and d), other transformations using the same metal have emerged as powerful tools for protein modification at different groups. Similarly to cross-metathesis, palladium-catalyzed cross-coupling of aryl halides or boronates with organometallic partners represents one the most useful methods for C–C bond formation, being awarded with the Nobel Prize in 2010.(179) Advantages of these methods include (i) high functional group tolerance, (ii) reduced toxicity, (iii) chemical bioorthogonality, (iv) the use of air- and moisture-stable ligands avoiding inert atmosphere or degassed solvents, and finally (v) stability of the product and irreversibility of the transformation, which make these transformations amenable and attractive protocols for generating stable protein conjugates (Schemes 22 and 23). Preliminary examples of Suzuki–Miyaura cross-couplings on a p-iodophenylalanine-encoded (pIPhe) peptide revealed the feasibility of this transformation using Na₂PdCl₄ with a series of boronic acid partners in a 1:1 mixture of glycerol and water, resulting in high conversions at 40 °C.(180) Early examples using pIPhe-encoded proteins included a Mizoroki–Heck reaction (alkene cross-coupling partner)(181) with a Pd(OAc)₂/TPPTS catalytic system (Scheme 22a) together with MgCl₂, which inhibits protein precipitation due to palladium binding, and a Sonogashira reaction (alkyne cross-coupling partner)(182) with Pd(OAc)₂/TPPTS and CuOTf (Scheme 22b). Conversions were, however, rather low (2–25%). A copper-free ligandless Sonogashira cross-coupling analogous, albeit less efficient, to that described in Scheme 20d also has been applied to the labeling of a GFP–pyrrolysine carrying a terminal iodophenyl group (up to 15% conversion with Na₂PdCl₄) (Scheme 22c).(167) The genetic incorporation of a boronate handle (Scheme 23) opened up an opportunity to perform Suzuki–Miyaura cross-couplings at this residue, however only with limited success (30% conversion with a fluorescent bodipy aryl iodide partner) using Pd₂(dba)₃. This is likely a result of the harsh reaction conditions employed (12 h at 70 °C).(183) These results highlight the need for the development of a general, mild Pd catalyst for such transformations.

Davis and co-workers contributed significantly to the use of palladium chemistry for protein modification strategies by employing water-soluble and air-stable 2-amino-4,6-dihydroxypyrimidine (ADHP) ligands for a phosphine-free Suzuki–Miyaura reaction (Scheme 22d), which afforded unprecedented complete conversions (>95%) with a model cysteine-alkylated protein bearing a p-I-benzyl handle.(184) This transformation occurred under mild conditions (up to 37 °C in aqueous media) without the need of a cosolvent in only 30 min. Indeed, a huge range of aryl and vinyl boronic acid cross-coupling partners were successfully employed, allowing the installation of biaryl moieties and glycosides.(184)

Recent progress include the expansion of such a reaction at genetically encoded pIPhe,(185) which revealed the importance of Pd scavenging with 3-mercaptopropionic acid to prevent protein precipitation or Cys interference, similarly to the role of MgCl₂ in early Mizoroki–Heck examples.(181) Other inherent issues associated with this transformation such as dehydrohalogenation remain a challenge. Finally, genetic encoding and a site-selective labeling approach for protein modification by Suzuki–Miyaura cross-coupling has been successfully applied for cell surface labeling in E. coli by attaching either fluorescent molecules(186) or glycosides, thus modulating the interaction of bacterial glycocalyx with several binding partners.(187) The covalent labeling of molecules on the bacterial cell surface was efficiently achieved via Suzuki–Miyaura chemistry after incorporation of pIPhe into the outer membrane channel protein C (OmpC) using an amber stop codon suppression technique. Cross-couplings with either a fluorophore or a sugar boronic acid/fluorescent lectin reporter were visualized by fluorescence microscopy, demonstrating a reduced toxicity at the catalyst loadings required for efficient labeling. Although Pd(OAc)₂·(ADHP)₂ catalysts have proved efficient in both Suzuki–Miyaura and copper-free Sonogashira cross-couplings, the use of alternative catalytic systems (e.g., N-heterocyclic carbene (NHC)–Pd catalysts for the cell surface labeling of mammalian cells) (Scheme 22d)(188) or the development of ligandless protocols such as the site-selective protein PEGylation by Suzuki–Miyaura cross-coupling recently (Scheme 22e) will be of enlarged value in particularly important biotechnology applications such as the development of therapeutic proteins with improved properties.(189)

4 Conclusion

ARTICLE SECTIONS

Jump To

This review has highlighted the state of the art of recent aqueous reaction methodology developed for site-selective chemical protein modification. The awareness of the need to develop site-selective protein modification methods is still recent. Despite several advances reported in the last 10 years, there remains a need for additional and complementary site-selective reactions with improved kinetics and selectivities. These methods will expand the current available chemical toolbox and help chemists and biologists further improve their understanding of complex biochemical processes. We anticipate a key role for metal-mediated transformations in protein chemistry and highlight challenges associated with adapting such chemistries to biological systems. These include (i) enlarging the plethora of metal-mediated transformations for protein modification by developing catalytic systems able to efficiently work in benign aqueous systems, at physiological temperature and pH, and in the presence of oxygen; (ii) progressing toward “real” catalytic systems because almost all metal-mediated strategies reported to date require an excess of metal to achieve moderate-to-good conversions (improve the catalyst turnover numbers); (iii) moving to interspecies couplings because most of the current metal-mediated protocols are limited to prokaryotic systems; (iv) designing and developing cell-permeable reagents and catalysts to perform intracellular reactions because most of the current methods are limited to cell lysate or surface labeling; and finally (v) addressing toxicity problems that may allow in vivo couplings with whole-body organisms. In addition, site-selective protein modification will be central for the preparation of the next generation of biopharmaceuticals, including ADCs for cancer therapy and glycoproteins for vaccination. Such approaches will lead to defined constructs that enable a clear molecular dissection of modified protein structure on therapeutic function(5a, 56a) and hopefully result in therapeutic candidates with improved safety and efficacy.

The authors declare no competing financial interest.

Acknowledgment

ARTICLE SECTIONS

Jump To

O.B. thanks the European Commission (Marie Curie CIG) and Ministerio de Ciencia e Innovación, Spain (Juan de la Cierva Fellowship). G.J.L.B. thanks his generous sources of funding: Royal Society, FCT Portugal (FCT Investigator), European Commission (Marie Curie CIG), and the EPSRC. G.J.L.B. is a Royal Society University Research Fellow. The authors thank Paula Boutureira Regla and Francisco Pinteus da Cruz Lopes Bernardes for inspiration.

References

ARTICLE SECTIONS

Jump To

This article references 189 other publications.

1
Stephanopoulos, N.; Francis, M. B. Nat. Chem. Biol. 2011, 7, 876
[ Crossref], [ PubMed], [ CAS], Google Scholar
1
Choosing an effective protein bioconjugation strategy
Stephanopoulos, Nicholas; Francis, Matthew B.
Nature Chemical Biology (2011), 7 (12), 876-884CODEN: NCBABT; ISSN:1552-4450. (Nature Publishing Group)
A review. The collection of chem. techniques that can be used to attach synthetic groups to proteins has expanded substantially in recent years. Each of these approaches allows new protein targets to be addressed, leading to advances in biol. understanding, new protein-drug conjugates, targeted medical imaging agents and hybrid materials with complex functions. The protein modification reactions in current use vary widely in their inherent site selectivity, overall yields and functional group compatibility. Some are more amenable to large-scale bioconjugate prodn., and a no. of techniques can be used to label a single protein in a complex biol. mixt. This review examines the way in which exptl. circumstances influence one's selection of an appropriate protein modification strategy. It also provides a simple decision tree that can narrow down the possibilities in many instances. The review concludes with example studies that examine how this decision process has been applied in different contexts.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhsVOisbbP&md5=f635776ca8c147f5e2e1227f8eec29d8
2
Walsh, C. T.; Garneau-Tsodikova, S.; Gregory J. Gatto, J. Angew. Chem., Int. Ed. 2005, 44, 7342
[ Crossref], [ PubMed], [ CAS], Google Scholar
2
Protein posttranslational modifications: The chemistry of proteome diversifications
Walsh, Christopher T.; Garneau-Tsodikova, Sylvie; Gatto, Gregory J., Jr.
Angewandte Chemie, International Edition (2005), 44 (45), 7342-7372CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
A review. The diversity of distinct covalent forms of proteins (the proteome) greatly exceeds the no. of proteins predicted by DNA coding capacities owing to directed post-translational modifications. Enzymes dedicated to such protein modifications include 500 human protein kinases, 150 protein phosphatases, and 500 proteases. The major types of protein covalent modifications, such as phosphorylation, acetylation, glycosylation, methylation, and ubiquitination, can be classified according to the type of amino acid side-chain modified, the category of the modifying enzyme, and the extent of reversibility. Chem. events such as protein splicing, green fluorescent protein (GFP) maturation, and proteasome autoactivation also represent post-translational modifications. An understanding of the scope and pattern of the many post-translational modifications in eukaryotic cells provides insight into the function and dynamics of proteome compns.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXhtlSms77N&md5=1e1ccf345916c39631a1cc83093de9b1
3
Kee, J.-M.; Muir, T. W. ACS Chem. Biol. 2011, 7, 44
[ ACS Full Text ], Google Scholar
There is no corresponding record for this reference.
4
Bernardes, G. J. L.; Chalker, J. M.; Davis, B. G. Chemical Protein Modification; Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim, Germany, 2010.
[ Crossref], Google Scholar
There is no corresponding record for this reference.
5
(a) Sun, S. B.; Schultz, P. G.; Kim, C. H. ChemBioChem. 2014, 15, 1721
[ Crossref], [ PubMed], [ CAS], Google Scholar
5a
Therapeutic Applications of an Expanded Genetic Code
Sun, Sophie B.; Schultz, Peter G.; Kim, Chan Hyuk
ChemBioChem (2014), 15 (12), 1721-1729CODEN: CBCHFX; ISSN:1439-4227. (Wiley-VCH Verlag GmbH & Co. KGaA)
A review. To date, over 100 noncanonical amino acids (ncAAs) have been genetically encoded in living cells in order to expand the functional repertoire of the canonical 20 amino acids. More recently, this technol. has been expanded to the field of protein therapeutics, where traditional chem. methods typically result in heterogeneous mixts. of proteins. The site-specific incorporation of ncAAs with orthogonal chem. groups allows unprecedented control over the site of conjugation and the stoichiometry, thus facilitating the rational optimization of the biol. functions and/or pharmacokinetics of biologics. Herein, we discuss the recent contribution of ncAA technol. in enhancing the pharmacol. properties of current protein therapeutics as well as developing novel therapeutic modalities.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtFyhu7nL&md5=e13618035c3ccc5bed06a3e6cf55b8fe
(b) Pelegri-O’Day, E. M.; Lin, E.-W.; Maynard, H. D. J. Am. Chem. Soc. 2014, 136, 14323
[ ACS Full Text ], [ CAS], Google Scholar
5b
Therapeutic Protein-Polymer Conjugates: Advancing Beyond PEGylation
Pelegri-O'Day, Emma M.; Lin, En-Wei; Maynard, Heather D.
Journal of the American Chemical Society (2014), 136 (41), 14323-14332CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
A review. Protein-polymer conjugates are widely used as therapeutics. All Food and Drug Administration (FDA)-approved protein conjugates are covalently linked to poly(ethylene glycol) (PEG). These PEGylated drugs have longer half-lives in the bloodstream, leading to less frequent dosing, which is a significant advantage for patients. However, there are some potential drawbacks to PEG that are driving the development of alternatives. Polymers that display enhanced pharmacokinetic properties along with addnl. advantages such as improved stability or degradability will be important to advance the field of protein therapeutics. This perspective presents a summary of protein-PEG conjugates for therapeutic use and alternative technologies in various stages of development as well as suggestions for future directions. Established methods of producing protein-PEG conjugates and new approaches utilizing controlled radical polymn. are also covered.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsFCjsLfI&md5=784f96a81f2c6f6bfba8b4dadb31bdcb
(c) Chari, R. V. J.; Miller, M. L.; Widdison, W. C. Angew. Chem., Int. Ed. 2014, 53, 3796
[ Crossref], [ PubMed], [ CAS], Google Scholar
5c
Antibody-Drug Conjugates: An Emerging Concept in Cancer Therapy
Chari, Ravi V. J.; Miller, Michael L.; Widdison, Wayne C.
Angewandte Chemie, International Edition (2014), 53 (15), 3796-3827CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
A review. Traditional cancer chemotherapy is often accompanied by systemic toxicity to the patient. Monoclonal antibodies against antigens on cancer cells offer an alternative tumor-selective treatment approach. However, most monoclonal antibodies are not sufficiently potent to be therapeutically active on their own. Antibody-drug conjugates (ADCs) use antibodies to deliver a potent cytotoxic compd. selectively to tumor cells, thus improving the therapeutic index of chemotherapeutic agents. The recent approval of two ADCs, brentuximab vedotin and ado-trastuzumab emtansine, for cancer treatment has spurred tremendous research interest in this field. This Review touches upon the early efforts in the field, and describes how the lessons learned from the first-generation ADCs have led to improvements in every aspect of this technol., i.e., the antibody, the cytotoxic compd., and the linker connecting them, leading to the current successes. The design of ADCs currently in clin. development, and results from mechanistic studies and preclin. and clin. evaluation are discussed. Emerging technologies that seek to further advance this exciting area of research are also discussed.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXjtVGmsr0%253D&md5=fbfb2f843f516654ea7c0eb98949604c
(d) Schumacher, D.; Hackenberger, C. P. R. Curr. Opin. Chem. Biol. 2014, 22, 62
[ Crossref], [ PubMed], [ CAS], Google Scholar
5d
More than add-on: chemoselective reactions for the synthesis of functional peptides and proteins
Schumacher, Dominik; Hackenberger, Christian PR
Current Opinion in Chemical Biology (2014), 22 (), 62-69CODEN: COCBF4; ISSN:1367-5931. (Elsevier B.V.)
The quest to enlarge the mol. space of functional biomols. has led to the discovery of selective, mild and high-yielding chem. reactions for the modification of peptides and proteins. These conjugation methods have recently become even more advanced with the advent of modern biochem. techniques such as unnatural protein expression or enzymic reactions that allow the site-specific modification of proteins. Within this overview, we will highlight recent examples that describe the site-specific functionalization of proteins. These examples go beyond the straightforward attachment of a given functional moiety to the protein backbone by employing either an innovative linker-design or by novel conjugation chem., where the modification reaction itself is responsible for the (altered) functional behavior of the biomol. The examples covered herein include 'turn-on' probes for cellular imaging with low levels of background fluorescence, branched or cleavable polymer-protein conjugates of high stability within a cellular environment, the installation of natural occurring posttranslational modifications to help understand their role in complex cellular environments and finally the engineering of novel antibody drug conjugates to facilitate target specific drug release.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhs12nur7J&md5=cb567453613d1b16eeb6d8303b3db3ba
6
(a) Siman, P.; Brik, A. Org. Biomol. Chem. 2012, 10, 5684
[ Crossref], [ PubMed], [ CAS], Google Scholar
6a
Chemical and semisynthesis of posttranslationally modified proteins
Siman, Peter; Brik, Ashraf
Organic & Biomolecular Chemistry (2012), 10 (30), 5684-5697CODEN: OBCRAK; ISSN:1477-0520. (Royal Society of Chemistry)
A review. Posttranslational modifications of proteins play crucial roles in health and disease by affecting numerous aspects of protein structure, function, stability and sub cellular localization. Yet understanding the effects of these modifications on several of these processes at the mol. level has been hindered by the lack of homogeneously modified proteins obtained via traditional biochem. and mol. biol. approaches. Moreover, the prepn. of such bioconjugates at a workable level is highly demanding. Recent advances in protein chem. applying chem. and semisynthetic approaches are becoming increasingly beneficial to overcome these challenges. These methods allow site-specific modifications of a desired protein and afford the product in large quantities for biochem. and structural analyses. In this review, the authors survey these efforts and their importance in dissecting the role of several posttranslational modifications in various proteins. Several examples are presented where glycosylated, phosphorylated, ubiquitinated, lipidated, acetylated and methylated proteins were prepd.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtVSmu7bO&md5=5d3d98ee85d9100e42a81035e65331be
(b) Kent, S. B. H. Chem. Soc. Rev. 2009, 38, 338
[ Crossref], [ PubMed], [ CAS], Google Scholar
6b
Total chemical synthesis of proteins
Kent, Stephen B. H.
Chemical Society Reviews (2009), 38 (2), 338-351CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)
A review. This tutorial review outlines the modern ligation methods that enable the efficient total chem. synthesis of enzymes and other protein mols. Key to this success is the chemoselective reaction of unprotected synthetic peptides ('chem. ligation'). Notably, native chem. ligation enables the reaction of two unprotected peptides in aq. soln. at neutral pH to form a single product in near quant. yield. Full-length synthetic polypeptides are folded to form the defined tertiary structure of the target protein mol., which is characterized by mass spectrometry, NMR, and x-ray crystallog., in addn. to biochem. and/or biol. activity.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXksVSntL8%253D&md5=ca6c6ab4e20f0e05d2b83b2fe1c19030
(c) Hackenberger, C. P. R.; Schwarzer, D. Angew. Chem., Int. Ed. 2008, 47, 10030
[ Crossref], [ PubMed], [ CAS], Google Scholar
6c
Chemoselective ligation and modification strategies for peptides and proteins
Hackenberger, Christian P. R.; Schwarzer, Dirk
Angewandte Chemie, International Edition (2008), 47 (52), 10030-10074CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
A review. The investigation of biol. processes by chem. methods, commonly referred to as chem. biol., often requires chem. access to biol. relevant macromols. such as peptides and proteins. Building upon solid-phase peptide synthesis, investigations have focused on the development of chemoselective ligation and modification strategies to link synthetic peptides or other functional units to larger synthetic and biol. relevant macromols. This review summarizes recent developments in the field of chemoselective ligation and modification strategies and illustrates their application, with examples ranging from the total synthesis of proteins to the semisynthesis of naturally modified proteins.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXislSitA%253D%253D&md5=7fc894096d44fb11c2c0187cc4fe79c7
7
Baslé, E.; Joubert, N.; Pucheault, M. Chem. Biol. 2010, 17, 213
[ Crossref], [ PubMed], [ CAS], Google Scholar
7
Protein Chemical Modification on Endogenous Amino Acids
Basle, Emmanuel; Joubert, Nicolas; Pucheault, Mathieu
Chemistry & Biology (Cambridge, MA, United States) (2010), 17 (3), 213-227CODEN: CBOLE2; ISSN:1074-5521. (Cell Press)
A review. Chem. modification of protein is an arduous but fruitful task. Many chem. methods have been developed for such purpose by carefully balancing reactivity and selectivity. Now both chemists and biologists have in hand an arsenal of tools from which they can select a relevant reaction to tackle their problems. This review focuses on the various chem. transformations available for selective modification of proteins. It also provides a brief overview of some of their main applications, including detection of protein interactions, prepn. of bioconjugates, and protein microarrays.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXjvFKhurY%253D&md5=82a023a2f4e96136205bdb19901bd401
8
(a) Tasdelen, M. A.; Yagci, Y. Angew. Chem., Int. Ed. 2013, 52, 5930
[ Crossref], [ PubMed], [ CAS], Google Scholar
8a
Light-Induced Click Reactions
Tasdelen, Mehmet Atilla; Yagci, Yusuf
Angewandte Chemie, International Edition (2013), 52 (23), 5930-5938CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
A review. Spatial and temporal control over chem. and biol. processes, both in terms of "tuning" products and providing site-specific control, is one of the most exciting and rapidly developing areas of modern science. For synthetic chemists, the challenge is to discover and develop selective and efficient reactions capable of generating useful mols. in a variety of matrixes. In recent studies, light has been recognized as a valuable method for detg. where, when, and to what extent a process is started or stopped. Accordingly, this Minireview will present the fundamental aspects of light-induced click reactions, highlight the applications of these reactions to diverse fields of study, and discuss the potential for this methodol. to be applied to the study of biomol. systems.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXntF2lsLY%253D&md5=19bac16930cc09dee72fcc1f0307befe
(b) Palomo, J. M. Org. Biomol. Chem. 2012, 10, 9309
[ Crossref], [ PubMed], [ CAS], Google Scholar
8b
Click reactions in protein chemistry: from the preparation of semisynthetic enzymes to new click enzymes
Palomo, Jose M.
Organic & Biomolecular Chemistry (2012), 10 (47), 9309-9318CODEN: OBCRAK; ISSN:1477-0520. (Royal Society of Chemistry)
A review. Click-chem. is an approach based on cycloaddn. reactions which has been successfully used as a chem. approach for complex org. mols. and which has recently starred in a boom in the world of protein chem. The advantage of the use of this technique in protein chem. is based on a very high and efficient chemoselectivity, which usually requires simple or no purifn. and is extremely rate-accelerated in aq. media. Here, the author discusses some of the most recent advances in the application of this reaction in selective enzyme surface modification for the creation of new semisynthetic enzymes (fluorescence labeled enzymes, peptide-enzyme conjugates, glycosylated enzymes), and interestingly, the recent design and creation of "click" enzymes.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xhs1yksL%252FO&md5=b50a62e468f8371886303df0c87bd04b
(c) van Berkel, S. S.; van Eldijk, M. B.; van Hest, J. C. M. Angew. Chem., Int. Ed. 2011, 50, 8806
[ Crossref], [ PubMed], [ CAS], Google Scholar
8c
Staudinger Ligation as a Method for Bioconjugation
van Berkel, Sander S.; van Eldijk, Mark B.; van Hest, Jan C. M.
Angewandte Chemie, International Edition (2011), 50 (38), 8806-8827CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
A review. In 1919 the German chemist Hermann Staudinger was the first to describe the reaction between an azide and a phosphine. It was not until recently, however, that Bertozzi and co-workers recognized the potential of this reaction as a method for bioconjugation and transformed it into the so-called Staudinger ligation. The bio-orthogonal character of both the azide and the phosphine functions resulted in the Staudinger ligation finding numerous applications in various complex biol. systems. For example, the Staudinger ligation has been used to label glycans, lipids, DNA, and proteins. Moreover, the Staudinger ligation has been used as a synthetic method to construct glycopeptides, microarrays, and functional biopolymers. In the emerging field of bio-orthogonal ligation strategies, the Staudinger ligation has set a high std. to which most of the new techniques are often compared. This review summarizes recent developments and new applications of the Staudinger ligation.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhtFWjsLrM&md5=dab931ed4005aeec679d5789fc778b0d
(d) Lallana, E.; Riguera, R.; Fernandez-Megia, E. Angew. Chem., Int. Ed. 2011, 50, 8794
[ Crossref], [ PubMed], [ CAS], Google Scholar
8d
Reliable and Efficient Procedures for the Conjugation of Biomolecules through Huisgen Azide-Alkyne Cycloadditions
Lallana, Enrique; Riguera, Ricardo; Fernandez-Megia, Eduardo
Angewandte Chemie, International Edition (2011), 50 (38), 8794-8804CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
A review. The CuI-catalyzed azide-alkyne cycloaddn. (CuAAC) has been established as a powerful coupling technol. for the conjugation of proteins, nucleic acids, and polysaccharides. Nevertheless, several shortcomings related to the presence of Cu, mainly oxidative degrdn. by reactive oxygen species and sample contamination by Cu, have been pointed out. This Minireview discusses key aspects found in the development of the efficient and benign functionalization of biomacromols. through CuAAC, as well as the Cu-free strain-promoted azide-alkyne cycloaddn. (SPAAC).
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhtVentbnF&md5=1c97cf8eb4e3dd99a31525ee4637f20b
9
(a) Villalonga, M. L.; Díez, P.; Sánchez, A.; Gamella, M.; Pingarrón, J. M.; Villalonga, R. Chem. Rev. 2014, 114, 4868
[ ACS Full Text ], [ CAS], Google Scholar
9a
Neoglycoenzymes
Villalonga, Maria L.; Diez, Paula; Sanchez, Alfredo; Gamella, Maria; Pingarron, Jose M.; Villalonga, Reynaldo
Chemical Reviews (Washington, DC, United States) (2014), 114 (9), 4868-4917CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)
A review. The rational design of proteins with desired functional properties by manipulation of their chem. compn. and three-dimensional structure is a challenge that has fascinated researchers in dierent disciplines during the last century. In this context, the ultimate goal of enzyme engineering has been to create novel and highly active enzymes with increased stability, selectivity, and substrate range, able to work in extreme physicochem. and biol. conditions. The coverage of this Review includes aspects concerning neoglycoenzyme synthesis, classification, structural and functional properties, and applications. For this purpose, reports ofoutstanding significance in neoglycoenzyme science will becritically discussed. A detailed description of the syntheticmethods used for prepg. protein glycoconjugates as well asthe properties and applications of these derivs. are beyond the scope of this Review and have been excellently covered in previous papers. Therefore, only the synthetic methods specifically adapted to enzyme artificial glycosylation will be discussed. This Review will highlight the new and/or improved properties showed by the artificial glycoenzymes as well as their most relevant applications. The predicted impact of neoglycoenzymes in new emerging research areas will be also encompassed.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhslygtro%253D&md5=b854da33b044abdaef75c0aaa75d2773
(b) Wang, L.-X.; Amin, M. N. Chem. Biol. 2014, 21, 51
[ Crossref], [ PubMed], [ CAS], Google Scholar
9b
Chemical and Chemoenzymatic Synthesis of Glycoproteins for Deciphering Functions
Wang, Lai-Xi; Amin, Mohammed N.
Chemistry & Biology (Oxford, United Kingdom) (2014), 21 (1), 51-66CODEN: CBOLE2; ISSN:1074-5521. (Elsevier Ltd.)
A review. Glycoproteins are an important class of biomols. involved in a no. of biol. recognition processes. However, natural and recombinant glycoproteins are usually produced as mixts. of glycoforms that differ in the structures of the pendent glycans, which are difficult to sep. in pure glycoforms. As a result, synthetic homogeneous glycopeptides and glycoproteins have become indispensable probes for detailed structural and functional studies. A no. of elegant chem. and biol. strategies have been developed for synthetic construction of tailor-made, full-size glycoproteins to address specific biol. problems. In this review, we highlight recent advances in chem. and chemoenzymic synthesis of homogeneous glycoproteins. Selected examples are given to demonstrate the applications of tailor-made, glycan-defined glycoproteins for deciphering glycosylation functions.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtF2htLk%253D&md5=da142c9aea24639867a2396b5fd17b9f
(c) Schmaltz, R. M.; Hanson, S. R.; Wong, C.-H. Chem. Rev. 2011, 111, 4259
[ ACS Full Text ], [ CAS], Google Scholar
9c
Enzymes in the Synthesis of Glycoconjugates
Schmaltz, Ryan M.; Hanson, Sarah R.; Wong, Chi-Huey
Chemical Reviews (Washington, DC, United States) (2011), 111 (7), 4259-4307CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)
A review. This review is intended to update our previous discussion on the chemoenzymic synthesis of carbohydrates and glycoconjugates, with new emphasis placed on enzymic and whole-cell engineering techniques for the prodn. of homogeneous glycoproteins. Glycans, the carbohydrate portion of glycoconjugates, have diverse structures and far-reaching biol. functions that remain to be elucidated. The need to understand glycans and glycoconjugates has motivated an extraordinary amt. of work toward developing synthetic and chemoenzymic methods to produce them in a pure form over the past ten years. While many of these routes have been the subject of focused reviews, this account provides a thorough resource of the chemoenzymic and whole-cell tools that are available for producing glycans and glycoconjugates with defined structures. Because the covered topics are broad, succinct discussions of key concepts are provided in the text along with a few representative examples, while more in-depth consideration of subjects can be gained by consulting the extensive sources to the primary literature provided throughout.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXosFymtbY%253D&md5=e5c2ef236283d58da086afe5ea571818
(d) Gamblin, D. P.; Scanlan, E. M.; Davis, B. G. Chem. Rev. 2009, 109, 131
[ ACS Full Text ], [ CAS], Google Scholar
9d
Glycoprotein Synthesis: An Update
Gamblin, David P.; Scanlan, Eoin M.; Davis, Benjamin G.
Chemical Reviews (Washington, DC, United States) (2009), 109 (1), 131-163CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)
A review. The developments in glycoprotein synthesis since 2002 are highlighted in this review. Topics of discussion are biol. importance of glycopeptide/glycoproteins, glycopeptide assembly and assembly strategies, chem. and enzymic methods for glycoprotein synthesis, mol. and cell biol. techniques in biosynthesis methods. This work includes strategies for synthesizing proteins as clin. biopharmaceuticals in the near future.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXhsFals7rI&md5=0bce8ff0722b4c57380bc12718255b33
10
Nischan, N.; Hackenberger, C. P. R. J. Org. Chem. 2014, 79, 10727
[ ACS Full Text ], [ CAS], Google Scholar
10
Site-specific PEGylation of Proteins: Recent Developments
Nischan, Nicole; Hackenberger, Christian P. R.
Journal of Organic Chemistry (2014), 79 (22), 10727-10733CODEN: JOCEAH; ISSN:0022-3263. (American Chemical Society)
A review. The attachment of linear polyethylene glycol (PEG) to peptides and proteins for their stabilization for in vivo applications is a milestone in pharmaceutical research and protein-drug development. However, conventional methods often lead to heterogeneous PEGylation mixts. with reduced protein activity. Current synthetic efforts aim to provide site-specific approaches by chemoselective targeting of canonical and noncanonical amino acids and to improve the PEG architecture. This synopsis highlights recent work in this area, which also resulted in improved pharmacokinetics of peptide and protein therapeutics.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhslOksr%252FJ&md5=7241ca75ef24af2dd0bffca520c4f6ea
11
(a) Matyjaszewski, K.; Tsarevsky, N. V. J. Am. Chem. Soc. 2014, 136, 6513
[ ACS Full Text ], [ CAS], Google Scholar
11a
Macromolecular Engineering by Atom Transfer Radical Polymerization
Matyjaszewski, Krzysztof; Tsarevsky, Nicolay V.
Journal of the American Chemical Society (2014), 136 (18), 6513-6533CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
A review. This Perspective presents recent advances in macromol. engineering enabled by ATRP. They include the fundamental mechanistic and synthetic features of ATRP with emphasis on various catalytic/initiation systems that use parts-per-million concns. of Cu catalysts and can be run in environmentally friendly media, e.g., water. The roles of the major components of ATRP-monomers, initiators, catalysts, and various additives-are explained, and their reactivity and structure are correlated. The effects of media and external stimuli on polymn. rates and control are presented. Some examples of precisely controlled elements of macromol. architecture, such as chain uniformity, compn., topol., and functionality, are discussed. Syntheses of polymers with complex architecture, various hybrids, and bioconjugates are illustrated. Examples of current and forthcoming applications of ATRP are covered. Future challenges and perspectives for macromol. engineering by ATRP are discussed.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXmslSrurY%253D&md5=a9277a80a8ad824041cdd4b19559d4cb
(b) Wallat, J. D.; Rose, K. A.; Pokorski, J. K. Polym. Chem. 2014, 5, 1545
[ Crossref], [ CAS], Google Scholar
11b
Proteins as substrates for controlled radical polymerization
Wallat, Jaqueline D.; Rose, Katie A.; Pokorski, Jonathan K.
Polymer Chemistry (2014), 5 (5), 1545-1558CODEN: PCOHC2; ISSN:1759-9962. (Royal Society of Chemistry)
A review. This review describes fundamental contributions in the area of proteins as macroinitiators and macro-chain transfer agents (CTA) for controlled radical polymn. (CRP). The review specifically highlights the concept of 'grafting-from' proteins, as new and efficient chem. has been developed to polymerize directly from protein substrates in aq. media. As the past ten years have shown, CRP has proven a powerful tool in the functionalization of proteins. This review considers the methods used to install protein based initiators and CTAs, the principle examples of ATRP and RAFT as polymn. methods, and finishes with more advanced methodologies such as the combination of genetic modifications and polymer chem., proteins as nanoparticles for drug delivery, and unnatural amino acid initiators.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhvFGhs78%253D&md5=89867bb09e64a24e5f2b5cb8fe8f7ae3
12
(a) King, M.; Wagner, A. Bioconjugate Chem. 2014, 25, 825
[ ACS Full Text ], [ CAS], Google Scholar
12a
Developments in the Field of Bioorthogonal Bond Forming Reactions-Past and Present Trends
King, Mathias; Wagner, Alain
Bioconjugate Chemistry (2014), 25 (5), 825-839CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
A review. In response to the ever increasing need of chem. biol. for new tools, a wide variety of new, highly selective reactions have been described. Herein we report a summary of recent developments and the historical background on bioorthogonal ligation reactions.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXmt1Gjsbs%253D&md5=c71e8c5fa752acc8c1285af1f18c60f7
(b) Lang, K.; Chin, J. W. Chem. Rev. 2014, 114, 4764
[ ACS Full Text ], [ CAS], Google Scholar
12b
Cellular Incorporation of Unnatural Amino Acids and Bioorthogonal Labeling of Proteins
Lang, Kathrin; Chin, Jason W.
Chemical Reviews (Washington, DC, United States) (2014), 114 (9), 4764-4806CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)
A review. A range of bioorthogonal reactions are described and methods discussed include the cellular cotranslational incorporation of unnatural amino acids bearing bioorthogonal functionalities into proteins via residue-specific or site-specific approaches. Applications of residue-specific incorporation and labeling and developments of site-specific incorporation and labeling are outlined.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXkslamtrY%253D&md5=bbb5b3099d3fccf801262e6b0d51676b
(c) Patterson, D. M.; Nazarova, L. A.; Prescher, J. A. ACS Chem. Biol. 2014, 9, 592
[ ACS Full Text ], [ CAS], Google Scholar
12c
Finding the Right (Bioorthogonal) Chemistry
Patterson, David M.; Nazarova, Lidia A.; Prescher, Jennifer A.
ACS Chemical Biology (2014), 9 (3), 592-605CODEN: ACBCCT; ISSN:1554-8929. (American Chemical Society)
A review. Bioorthogonal chemistries can be used to tag diverse classes of biomols. in cells and other complex environments. With over 20 unique transformations now available, though, selecting an appropriate reaction for a given expt. is challenging. The authors compare and contrast the most common classes of bioorthogonal chemistries and provide a framework for matching the reactions with downstream applications. The authors also discuss ongoing efforts to identify novel biocompatible reactions and methods to control their reactivity. The continued expansion of the bioorthogonal toolkit will provide new insights into biomol. networks and functions and thus refine the authors' understanding of living systems.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXpt1Ohtg%253D%253D&md5=d65dabc417be90fa15af42e97cbd0422
(d) Lang, K.; Chin, J. W. ACS Chem. Biol. 2014, 9, 16
[ ACS Full Text ], [ CAS], Google Scholar
12d
Bioorthogonal Reactions for Labeling Proteins
Lang, Kathrin; Chin, Jason W.
ACS Chemical Biology (2014), 9 (1), 16-20CODEN: ACBCCT; ISSN:1554-8929. (American Chemical Society)
A review. Bioorthogonal reactions for labeling proteins in vitro, on the cell surface and inside living cells are discussed. Some of the reactions discussed include Staudinger ligations, alkyne-azide cycloaddn., metal-catalyzed reactions, aminothiol condensations, light-induced dipolar cycloaddn. reaction and Diels-Alder reactions.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXmsVShuw%253D%253D&md5=62049f6d20016cfa62c4ad34d63dcec6
(e) Takaoka, Y.; Ojida, A.; Hamachi, I. Angew. Chem., Int. Ed. 2013, 52, 4088
[ Crossref], [ PubMed], [ CAS], Google Scholar
12e
Protein Organic Chemistry and Applications for Labeling and Engineering in Live-Cell Systems
Takaoka, Yousuke; Ojida, Akio; Hamachi, Itaru
Angewandte Chemie, International Edition (2013), 52 (15), 4088-4106CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
A review. The modification of proteins with synthetic probes is a powerful means of elucidating and engineering the functions of proteins both in vitro and in live cells or in vivo. Herein the authors review recent progress in chem.-based protein modification methods and their application in protein engineering, with particular emphasis on the following four strategies: (1) the bioconjugation reactions of amino acids on the surfaces of natural proteins, mainly applied in test-tube settings; (2) the bioorthogonal reactions of proteins with non-natural functional groups; (3) the coupling of recognition and reactive sites using an enzyme or short peptide tag-probe pair for labeling natural amino acids; and (4) ligand-directed labeling chemistries for the selective labeling of endogenous proteins in living systems. Overall, these techniques represent a useful set of tools for application in chem. biol., with the methods 2-4 in particular being applicable to crude (living) habitats. Although still in its infancy, the use of org. chem. for the manipulation of endogenous proteins, with subsequent applications in living systems, represents a worthy challenge for many chemists.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXivVKhsLY%253D&md5=9f7ef6846cc3e64f802254bd25d25941
(f) Debets, M. F.; van Hest, J. C. M.; Rutjes, F. P. J. T. Org. Biomol. Chem. 2013, 11, 6439
[ Crossref], [ PubMed], [ CAS], Google Scholar
12f
Bioorthogonal labelling of biomolecules: new functional handles and ligation methods
Debets, Marjoke F.; van Hest, Jan C. M.; Rutjes, Floris P. J. T.
Organic & Biomolecular Chemistry (2013), 11 (38), 6439-6455CODEN: OBCRAK; ISSN:1477-0520. (Royal Society of Chemistry)
This review provides a literature overview of bioorthogonal ligation methods for protein modification, which have largely evolved over the last 15 years. Since 1990, various new reactions have been developed that do not involve naturally occurring functional handles. Esp. the development of such so-called bioorthogonal ligations has significantly contributed to our ability to selectively modify biomols. not only in the test tube, but also in living systems.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhsVCjtL7I&md5=61856d4d5fe81c40a1657f1f23c1aff7
(g) Ramil, C. P.; Lin, Q. Chem. Commun. 2013, 49, 11007
[ Crossref], [ PubMed], [ CAS], Google Scholar
12g
Bioorthogonal chemistry: strategies and recent developments
Ramil, Carlo P.; Lin, Qing
Chemical Communications (Cambridge, United Kingdom) (2013), 49 (94), 11007-11022CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
A review. The use of covalent chem. to track biomols. in their native environment-a focus of bioorthogonal chem.-has received considerable interest recently among chem. biologists and org. chemists alike. To facilitate wider adoption of bioorthogonal chem. in biomedical research, a central effort in the last few years has been focused on the optimization of a few known bioorthogonal reactions, particularly with respect to reaction kinetics improvement, novel genetic encoding systems, and fluorogenic reactions for bioimaging. During these optimizations, three strategies have emerged, including the use of ring strain for substrate activation in the cycloaddn. reactions, the discovery of new ligands and privileged substrates for accelerated metal-catalyzed reactions, and the design of substrates with pre-fluorophore structures for rapid "turn-on" fluorescence after selective bioorthogonal reactions. In addn., new bioorthogonal reactions based on either modified or completely unprecedented reactant pairs have been reported. Finally, increasing attention has been directed toward the development of mutually exclusive bioorthogonal reactions and their applications in multiple labeling of a biomol. in cell culture. In this feature article, the authors wish to present the recent progress in bioorthogonal reactions through the selected examples that highlight the above-mentioned strategies. Considering increasing sophistication in bioorthogonal chem. development, the authors strive to project several exciting opportunities where bioorthogonal chem. can make a unique contribution to biol. in the near future.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhslWls7vL&md5=55e8bcb626cf7d28ea9937a8fe800ca8
(h) Sletten, E. M.; Bertozzi, C. R. Angew. Chem., Int. Ed. 2009, 48, 6974
[ Crossref], [ PubMed], [ CAS], Google Scholar
12h
Bioorthogonal Chemistry: Fishing for Selectivity in a Sea of Functionality
Sletten, Ellen M.; Bertozzi, Carolyn R.
Angewandte Chemie, International Edition (2009), 48 (38), 6974-6998CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
A review. The study of biomols. in their native environments is a challenging task because of the vast complexity of cellular systems. Technologies developed in the last few years for the selective modification of biol. species in living systems have yielded new insights into cellular processes. Key to these new techniques are bioorthogonal chem. reactions, whose components must react rapidly and selectively with each other under physiol. conditions in the presence of the plethora of functionality necessary to sustain life. Herein the authors describe the bioorthogonal chem. reactions developed to date and how they can be used to study biomols.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXhtV2ltrvK&md5=993199cb4deabc186848bae6fe81f605
(i) Shih, H.-W.; Kamber, D. N.; Prescher, J. A. Curr. Opin. Chem. Biol. 2014, 21, 103
[ Crossref], [ PubMed], [ CAS], Google Scholar
12i
Building better bioorthogonal reactions
Shih, Hui-Wen; Kamber, David N.; Prescher, Jennifer A.
Current Opinion in Chemical Biology (2014), 21 (), 103-111CODEN: COCBF4; ISSN:1367-5931. (Elsevier B.V.)
A review. Over the past two decades, there has been intense interest in designing and implementing selective (bioorthogonal) reactions for biomol. tracking. Here we review the most widely used bioorthogonal chemistries in live cells and animals, drawing particular attention to the unique functional groups underlying these transformations. We also describe recent efforts to tune functional group reactivities and stabilities to access even more rapid and selective chemistries. Last, we highlight ongoing challenges in identifying new bioorthogonal reagents and combinations of reactions that can be used concurrently to tag multiple biomols.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtleis7vK&md5=f74ddb8b84c289deb9b1985add394dbb
(j) McKay, C. S.; Finn, M. G. Chem. Biol. 2014, 21, 1075
[ Crossref], [ PubMed], [ CAS], Google Scholar
12j
Click Chemistry in Complex Mixtures: Bioorthogonal Bioconjugation
McKay, Craig S.; Finn, M. G.
Chemistry & Biology (Oxford, United Kingdom) (2014), 21 (9), 1075-1101CODEN: CBOLE2; ISSN:1074-5521. (Elsevier Ltd.)
A review. The selective chem. modification of biol. mols. drives a good portion of modern drug development and fundamental biol. research. While a few early examples of reactions that engage amine and thiol groups on proteins helped establish the value of such processes, the development of reactions that avoid most biol. mols. so as to achieve selectivity in desired bond-forming events has revolutionized the field. We provide an update on recent developments in bioorthogonal chem. that highlights key advances in reaction rates, biocompatibility, and applications. While not exhaustive, we hope this summary allows the reader to appreciate the rich continuing development of good chem. that operates in the biol. setting.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsFyrur7N&md5=64a6e5ea8a232b97fce61d1268093fe4
(k) Spicer, C. D.; Davis, B. G. Nat. Commun. 2014, 5, 4740
[ Crossref], [ PubMed], [ CAS], Google Scholar
12k
Selective chemical protein modification
Spicer, Christopher D.; Davis, Benjamin G.
Nature Communications (2014), 5 (), 4740CODEN: NCAOBW; ISSN:2041-1723. (Nature Publishing Group)
The chem. modification of proteins is an important tool for probing natural systems and synthesizing novel conjugates. Here, Spicer and Davis review the merits and limitations of the most useful methods for selective modification at both natural and unnatural amino acids.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXksVeksb4%253D&md5=055c882ff0405b0bbb91edca3bcef8cb
13
Chalker, J. M.; Bernardes, G. J. L.; Lin, Y. A.; Davis, B. G. Chem.—Asian J. 2009, 4, 630
[ Crossref], [ PubMed], [ CAS], Google Scholar
13
Chemical modification of proteins at cysteine: opportunities in chemistry and biology
Chalker, Justin M.; Bernardes, Goncalo J. L.; Lin, Yuya A.; Davis, Benjamin G.
Chemistry - An Asian Journal (2009), 4 (5), 630-640CODEN: CAAJBI; ISSN:1861-4728. (Wiley-VCH Verlag GmbH & Co. KGaA)
A review. Chem. modification of proteins is a rapidly expanding area in chem. biol. Selective installation of biochem. probes has led to a better understanding of natural protein modification and macromol. function. In other cases such chem. alterations have changed the protein function entirely. Addnl., tethering therapeutic cargo to proteins has proven invaluable in campaigns against disease. For controlled, selective access to such modified proteins, a unique chem. handle is required. Cysteine, with its unique reactivity, has long been used for such modifications. Cysteine has enjoyed wide-spread use in selective protein modification, yet new applications and even new reactions continue to emerge. This Focus Review highlights the enduring utility of cysteine in protein modification with special focus on recent innovations in chem. and biol. assocd. with such modifications.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXmvVaisLk%253D&md5=ff4c5cc1590ec98c0f22f168a9320fcd
14
Hemantha, H. P.; Bavikar, S. N.; Herman-Bachinsky, Y.; Haj-Yahya, N.; Bondalapati, S.; Ciechanover, A.; Brik, A. J. Am. Chem. Soc. 2014, 136, 2665
[ ACS Full Text ], [ CAS], Google Scholar
14
Nonenzymatic Polyubiquitination of Expressed Proteins
Hemantha, Hosahalli P.; Bavikar, Sudhir N.; Herman-Bachinsky, Yifat; Haj-Yahya, Najat; Bondalapati, Somasekhar; Ciechanover, Aaron; Brik, Ashraf
Journal of the American Chemical Society (2014), 136 (6), 2665-2673CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
Ubiquitination is one of the most ubiquitous posttranslational modifications in eukaryotes and is involved in various cellular events such as proteasomal degrdn. and DNA repair. The overwhelming majority of studies aiming to understand ubiquitination and deubiquitination have employed unanchored ubiquitin chains and mono-ubiquitinated proteins. To shed light on these processes at the mol. level, it is crucial to have facile access to ubiquitin chains linked to protein substrates. Such conjugates are highly difficult to prep. homogenously and in workable quantities using the enzymic machinery. To address this formidable challenge we developed new chem. approaches to covalently attach ubiquitin chains to a protein substrate through its Cys residue. A key aspect of this approach is the installation of acyl hydrazide functionality at the C-terminus of the proximal Ub, which allows, after ubiquitin chain assembly, the introduction of various reactive electrophiles for protein conjugation. Employing α-globin as a model substrate, we demonstrate the facile conjugation to K48-linked ubiquitin chains, bearing up to four ubiquitins, through disulfide and thioether linkages. These bioconjugates were examd. for their behavior with the USP2 enzyme, which was found to cleave the ubiquitin chain in a similar manner to unanchored ones. Furthermore, proteasomal degrdn. study showed that di-ubiquitinated α-globin is rapidly degraded in contrast to the mono-ubiquitinated counterpart, highlighting the importance of the chain lengths on proteasomal degrdn. The present work opens unprecedented opportunities in studying the ubiquitin signal by enabling access to site-specifically polyubiquitinated proteins with an increased size and complexity.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXpslKjtg%253D%253D&md5=7a8a3abf522f486dd23c46a966b1c21a
15
(a) Massa, S.; Xavier, C.; De Vos, J.; Caveliers, V.; Lahoutte, T.; Muyldermans, S.; Devoogdt, N. Bioconjugate Chem. 2014, 25, 979
[ ACS Full Text ], [ CAS], Google Scholar
15a
Site-Specific Labeling of Cysteine-Tagged Camelid Single-Domain Antibody-Fragments for Use in Molecular Imaging
Massa, Sam; Xavier, Catarina; De Vos, Jens; Caveliers, Vicky; Lahoutte, Tony; Muyldermans, Serge; Devoogdt, Nick
Bioconjugate Chemistry (2014), 25 (5), 979-988CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
Site-specific labeling of mol. imaging probes allows the development of a homogeneous tracer population. The resulting batch-to-batch reproducible pharmacokinetic and pharmacodynamic properties are of great importance for clin. translation. Camelid single-domain antibody-fragments (sdAbs)-the recombinantly produced antigen-binding domains of heavy-chain antibodies, also called Nanobodies-are proficient probes for mol. imaging. To safeguard their intrinsically high binding specificity and affinity and to ensure the tracer's homogeneity, we developed a generic strategy for the site-specific labeling of sdAbs via a thio-ether bond. The unpaired cysteine was introduced at the carboxyl-terminal end of the sdAb to eliminate the risk of antigen binding interference. The spontaneous dimerization and capping of the unpaired cysteine required a redn. step prior to conjugation. This was optimized with the mild reducing agent 2-mercaptoethylamine in order to preserve the domain's stability. As a proof-of-concept the reduced probe was subsequently conjugated to maleimide-DTPA, for labeling with indium-111. A single conjugated tracer was obtained and confirmed via mass spectrometry. The specificity and affinity of the new sdAb-based imaging probe was validated in a mouse xenograft tumor model using a modified clin. lead compd. targeting the human epidermal growth factor receptor 2 (HER2) cancer biomarker. These data provide a versatile and standardized strategy for the site-specific labeling of sdAbs. The conjugation to the unpaired cysteine results in the prodn. of a homogeneous group of tracers and is a multimodal alternative to the technetium-99m labeling of sdAbs.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXmslOqsr0%253D&md5=ea61ec2fd78ba6096f3097272ade36e9
(b) Morales-Sanfrutos, J.; Lopez-Jaramillo, J.; Ortega-Munoz, M.; Megia-Fernandez, A.; Perez-Balderas, F.; Hernandez-Mateo, F.; Santoyo-Gonzalez, F. Org. Biomol. Chem. 2010, 8, 667
[ Crossref], [ PubMed], [ CAS], Google Scholar
15b
Vinyl sulfone: a versatile function for simple bioconjugation and immobilization
Morales-Sanfrutos, Julia; Lopez-Jaramillo, Javier; Ortega-Munoz, Mariano; Megia-Fernandez, Alicia; Perez-Balderas, Francisco; Hernandez-Mateo, Fernando; Santoyo-Gonzalez, Francisco
Organic & Biomolecular Chemistry (2010), 8 (3), 667-675CODEN: OBCRAK; ISSN:1477-0520. (Royal Society of Chemistry)
The authors report here on the capabilities of the vinyl sulfone function for the covalent coupling of proteins to detection labels, other biomols. and solid supports by exploiting the Michael-type addn. of this function to the amine-contg. residues, in conditions that preserve the functionality and biol. integrity of those biol. macromols. The easy functionalization of tags and solid supports with the vinyl sulfone function is a valuable tool in omic sciences that allows their coupling with the amine and thiol groups present in the proteogenic residues of proteins, in mild and green conditions compatible with their biol. function.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXnsV2qtg%253D%253D&md5=398fa4786531ec2eb89794476bda4012
(c) Morales-Sanfrutos, J.; Lopez-Jaramillo, F. J.; Hernandez-Mateo, F.; Santoyo-Gonzalez, F. J. Org. Chem. 2010, 75, 4039
[ ACS Full Text ], [ CAS], Google Scholar
15c
Vinyl Sulfone Bifunctional Tag Reagents for Single-Point Modification of Proteins
Morales-Sanfrutos, Julia; Lopez-Jaramillo, Francisco Javier; Hernandez-Mateo, Fernando; Santoyo-Gonzalez, Francisco
Journal of Organic Chemistry (2010), 75 (12), 4039-4047CODEN: JOCEAH; ISSN:0022-3263. (American Chemical Society)
The introduction of multiple labels onto biomols. is a challenge. The authors report herein the synthesis of vinyl sulfone derivatized bifunctional tag single-attachment-point reagents (BTSAP) bearing biotin and a fluorescent tag and their applications in proteins for the introduction of multiple labels by the Michael-type addn. of the electrophilic vinyl sulfone group. These BTSAP reagents were easily synthesized by a two-step chem. strategy involving the prepn. of alkyne vinyl sulfone derivatized tags (AVST) and subsequent click CuAAC attachment of a second azide functionalized tag. The direct coupling of BTSAP reagents with the low reactive protein horseradish peroxidase (HRP) turned it into a dual reporter group (i.e., fluorescence and peroxidase activity) that may be coupled to any recognition system via biotin-avidin affinity. The AVST compds. are not mere synthetic intermediates for the prepn. of BTSAP reagents but valuable clickable self-reporting compds. that allow the simultaneous introduction in proteins of an alkyne function and labeling when conjugated via the vinyl sulfone group. The implementation of these clickable AVST compds. in a CuAAC-based sequential approach also allows attainment of the dual labeling of HRP. This approach yields equiv. results in terms of fluorescent labeling, specific activity, and functionality of the biotin tag when compared with the direct bifunctional labeling by the BTSAP reagent. However, for life science this direct approach is more convenient since it avoids the use of copper catalysis, overcoming the toxicity drawback of this metal in biol. systems.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXmsVGjtLc%253D&md5=f2e96b4e9528959fec044d12a4b92b0d
16
Cal, P. M. S. D.; Bernardes, G. J. L.; Gois, P. M. P. Angew. Chem., Int. Ed. 2014, 53, 10585
[ Crossref], [ PubMed], [ CAS], Google Scholar
16
Cysteine-Selective Reactions for Antibody Conjugation
Cal, Pedro M. S. D.; Bernardes, Goncalo J. L.; Gois, Pedro M. P.
Angewandte Chemie, International Edition (2014), 53 (40), 10585-10587CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
A review. The unique targeting ability of antibodies has triggered burgeoning interest in the attachment of potent cytotoxic drugs onto these biomols. to create antibody-drug conjugates (ADCs). A key factor in the design of therapeutically useful ADCs is the ability to create chem. defined, stable protein-drug conjugates. The aim of this highlight is to discuss new methods for site-selective bioconjugation at native or engineered cysteines, methods which may be used to build homogeneous and stable ADCs.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXht1ams7jF&md5=a9b477a09aa18c06fa325db95184e436
17
Badescu, G.; Bryant, P.; Swierkosz, J.; Khayrzad, F.; Pawlisz, E.; Farys, M.; Cong, Y.; Muroni, M.; Rumpf, N.; Brocchini, S.; Godwin, A. Bioconjugate Chem. 2013, 25, 460
[ ACS Full Text ], Google Scholar
There is no corresponding record for this reference.
18
(a) Bailey, J. J.; Bundle, D. R. Org. Biomol. Chem. 2014, 12, 2193
[ Crossref], [ PubMed], [ CAS], Google Scholar
18a
Synthesis of high-mannose 1-thio glycans and their conjugation to protein
Bailey, Justin J.; Bundle, David R.
Organic & Biomolecular Chemistry (2014), 12 (14), 2193-2213CODEN: OBCRAK; ISSN:1477-0520. (Royal Society of Chemistry)
The oligosaccharides Man4 and Man5, substructures of the high-mannose glycans of HIV glycoprotein gp120, were synthesized with a terminal 1-thiomannopyranose residue. The anomeric thiol can be readily converted to an azidomethyl aglycon through reaction with dichloromethane and displacement with sodium azide. The resulting oligomannans were then conjugated to ubiquitin utilizing thiol alkylation or azide/alkyne reactive tethers of minimal length. By combining high efficiency conjugation reactions and a short tether, we sought to establish conjugation conditions that would permit high d. clustering of oligomannans in conjugate vaccines that could produce antibodies able to bind gp120 and potentially neutralize virus. LC-UV-MS was used to sep., identify and quantify the ubiquitin glycoconjugates with differing degrees of oligomannan incorporation. Binding of the HIV protective monoclonal antibody 2G12 and Con A to microtitre plates coated with glycoconjugates was measured by ELISA.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXktF2mtb0%253D&md5=1f8db49f9e037175bb8efbff1d0075b0
(b) Wurm, F. R.; Klok, H.-A. Chem. Soc. Rev. 2013, 42, 8220
[ Crossref], [ PubMed], [ CAS], Google Scholar
18b
Be squared: expanding the horizon of squaric acid-mediated conjugations
Wurm, Frederik R.; Klok, Harm-Anton
Chemical Society Reviews (2013), 42 (21), 8220-8236CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)
A review. Squaric acid diesters can be applied as reagents to couple two amino-functional compds. Consecutive coupling of two amines allows the synthesis of asym. squaric acid bisamides with either low mol. wt. compds. but also biomols. or polymers. The key feature of the squaric acid diester mediated coupling is the reduced reactivity of the resulting ester-amide after the first amidation step of the diester. This allows the sequential amidation and generation of asym. squaramides with high selectivity and in high yields. This article gives an overview of the well-established squaric acid diester mediated coupling reactions for glycoconjugates and presents recent advances that aim to expand this very versatile reaction protocol to the modification of peptides and proteins.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhsFOitrzJ&md5=456989efee4f9e7fc6ff08d9ac44e11f
(c) Patel, M. K.; Vijayakrishnan, B.; Koeppe, J. R.; Chalker, J. M.; Doores, K. J.; Davis, B. G. Chem. Commun. 2010, 46, 9119
[ Crossref], [ PubMed], [ CAS], Google Scholar
18c
Analysis of the dispersity in carbohydrate loading of synthetic glycoproteins using MALDI-TOF mass spectrometry
Patel, Mitul K.; Vijayakrishnan, Balakumar; Koeppe, Julia R.; Chalker, Justin M.; Doores, Katie J.; Davis, Benjamin G.
Chemical Communications (Cambridge, United Kingdom) (2010), 46 (48), 9119-9121CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
Statistical correlation of mass spectrum peak broadening with product dispersity in protein conjugation reactions allows more detailed characterization of putative therapeutic conjugates.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhsVynurbN&md5=831ffe2c13f1d8f7a9fc2be3478a41f6
(d) Liu, Z.; Liu, T.; Lin, Q.; Bao, C.; Zhu, L. Chem. Commun. 2014, 50, 1256
[ Crossref], [ PubMed], [ CAS], Google Scholar
18d
Photoreleasable thiol chemistry for facile and efficient bioconjugation
Liu, Zhenzhen; Liu, Tao; Lin, Qiuning; Bao, Chunyan; Zhu, Linyong
Chemical Communications (Cambridge, United Kingdom) (2014), 50 (10), 1256-1258CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
A facile methodol. for light-triggered release of thiols under mild conditions is presented, which can be utilized for in situ bioconjugation with protein and quantum dot nanoparticles (QDs) efficiently.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXjtVWltg%253D%253D&md5=e293bbc7ba5261c3aa4f781b29127eea
19
Asano, S.; Patterson, J. T.; Gaj, T.; Barbas, C. F. Angew. Chem., Int. Ed. 2014, 53, 11783
[ Crossref], [ PubMed], [ CAS], Google Scholar
19
Site-selective labeling of a lysine residue in human serum albumin
Asano, Shigehiro; Patterson, James T.; Gaj, Thomas; Barbas, Carlos F., III
Angewandte Chemie, International Edition (2014), 53 (44), 11783-11786CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
Conjugation to human serum albumin (HSA) has emerged as a powerful approach for extending the in vivo half-life of many small mol. and peptide/protein drugs. Current HSA conjugation strategies, however, can often yield heterogeneous mixts. with inadequate pharmacokinetics, low efficacies, and variable safety profiles. Here, we designed and synthesized analogs of TAK-242, a small mol. inhibitor of Toll-like receptor 4, that primarily reacted with a single lysine residue of HSA. These TAK-242-based cyclohexene compds. demonstrated robust reactivity, and Lys64 was identified as the primary conjugation site. A bivalent HSA conjugate was also prepd. in a site-specific manner. Addnl., HSA-cyclohexene conjugates maintained higher levels of stability both in human plasma and in mice than the corresponding maleimide conjugates. This new conjugation strategy promises to broadly enhance the performance of HSA conjugates for numerous applications.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsV2ntrfO&md5=e5dee953030a7fb53e28f3b88915a852
20
Adamo, R.; Nilo, A.; Castagner, B.; Boutureira, O.; Berti, F.; Bernardes, G. J. L. Chem. Sci. 2013, 4, 2995
[ Crossref], [ PubMed], [ CAS], Google Scholar
20
Synthetically defined glycoprotein vaccines: current status and future directions
Adamo, Roberto; Nilo, Alberto; Castagner, Bastien; Boutureira, Omar; Berti, Francesco; Bernardes, Goncalo J. L.
Chemical Science (2013), 4 (8), 2995-3008CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)
A review. Primary examples in vaccine design have shown good levels of carbohydrate-specific antibody generation when raised using extd. or fully synthetic capsular polysaccharide glycans covalently coupled to a protein carrier. Herein, the authors cover recent clin. developments of carbohydrate-based vaccines and describe how novel cutting-edge methodol. for the total synthesis of oligosaccharides and for the precise placement of carbohydrates at pre-detd. sites within a protein may be used to further improve the safety and efficacy of glycovaccines.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtVehs7jN&md5=eb09336f0a6302efb364de7539fd94a4
21
Crotti, S.; Zhai, H.; Zhou, J.; Allan, M.; Proietti, D.; Pansegrau, W.; Hu, Q.-Y.; Berti, F.; Adamo, R. ChemBioChem 2014, 15, 836
[ Crossref], [ PubMed], [ CAS], Google Scholar
21
Defined Conjugation of Glycans to the Lysines of CRM197 Guided by their Reactivity Mapping
Crotti, Stefano; Zhai, Huili; Zhou, Jing; Allan, Martin; Proietti, Daniela; Pansegrau, Werner; Hu, Qi-Ying; Berti, Francesco; Adamo, Roberto
ChemBioChem (2014), 15 (6), 836-843CODEN: CBCHFX; ISSN:1439-4227. (Wiley-VCH Verlag GmbH & Co. KGaA)
Systematic characterization of the reactivity of the lysine moieties in CRM197 towards N-hydroxysuccinimide linkers bearing alkynes or azides is described. This involves two-step conjugation of various glycans to CRM197 by click chem. in a well-defined manner. By semiquant. LC-MS/MS anal. of proteolytic digests of the conjugates formed, the reactivity of lysine residues in the protein was mapped and ranked. Computational anal. of the solvent accessibility of each lysine residue (based on the CRM197 crystal structure) established a correlation between reactivity and surface exposure. By this approach, conjugation involving lysine residues (normally a random process) can be controlled. It enables the prepn. of lysine-mediated glycoconjugates with improved batch-to-batch reproducibility, thereby producing neo-glycoconjugates with more-consistent biol. activity.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXjvVyrurk%253D&md5=2c5f51f81d507458a45b6467fda0c519
22
Chen, X.; Muthoosamy, K.; Pfisterer, A.; Neumann, B.; Weil, T. Bioconjugate Chem. 2012, 23, 500
[ ACS Full Text ], [ CAS], Google Scholar
22
Site-Selective Lysine Modification of Native Proteins and Peptides via Kinetically Controlled Labeling
Chen, Xi; Muthoosamy, Kasturi; Pfisterer, Anne; Neumann, Boris; Weil, Tanja
Bioconjugate Chemistry (2012), 23 (3), 500-508CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
The site-selective modification of the proteins RNase A, lysozyme C, and the peptide hormone somatostatin is presented via a kinetically controlled labeling approach. A single lysine residue on the surface of these biomols. reacts with an activated biotinylation reagent at mild conditions, physiol. pH, and at RT in a high yield of over 90%. In addn., fast reaction speed, quick and easy purifn., as well as low reaction temps. are particularly attractive for labeling sensitive peptides and proteins. Furthermore, the multifunctional bioorthogonal bioconjugation reagent (I) has been achieved allowing the site-selective incorporation of a single ethynyl group. The introduced ethynyl group is accessible for, e.g., click chem. as demonstrated by the reaction of RNase A with azidocoumarin. The approach reported herein is fast, less labor-intensive and minimizes the risk for protein misfolding. Kinetically controlled labeling offers a high potential for addressing a broad range of native proteins and peptides in a site-selective fashion and complements the portfolio of recombinant techniques or chemoenzymic approaches.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XitlOlt78%253D&md5=829098df917ba084086466464e585ae5
23
del Castillo, T.; Morales-Sanfrutos, J.; Santoyo-González, F.; Magez, S.; Lopez-Jaramillo, F. J.; Garcia-Salcedo, J. A. ChemMedChem 2014, 9, 383
[ Crossref], [ PubMed], [ CAS], Google Scholar
23
Monovinyl Sulfone β-Cyclodextrin. A Flexible Drug Carrier System
del Castillo, Teresa; Marales-Sanfrutos, Julia; Santoyo-Gonzalez, Francisco; Magez, Stefan; Lopez-Jaramillo, F. Javier; Garcia-Salcedo, Jose A.
ChemMedChem (2014), 9 (2), 383-389CODEN: CHEMGX; ISSN:1860-7179. (Wiley-VCH Verlag GmbH & Co. KGaA)
Cyclodextrins have been conjugated to target various receptors and have also been functionalized with carbohydrates for targeting specific organs. However, this approach is based on a rigid design that implies the ad hoc synthesis of each cyclodextrin-targeting agent conjugate. We hypothesized that: 1) a modular design that decouples the carrier function from the targeting function leads to a flexible system, 2) combining the reactivity of the vinyl sulfone group toward biomols. that act as targeting agents with the ability of cyclodextrin to form complexes with a wide range of drugs may yield a versatile system that allows the targeting of different organs with different drugs, and 3) the higher reactivity of histidine residues toward the vinyl sulfone group can be exploited to couple the cyclodextrin to the targeting system with a degree of regioselectivity. As a proof of concept, we synthesized a monovinyl sulfone β-cyclodextrin (module responsible for the payload), which, after coupling to recombinant antibody fragments raised against Trypanosoma brucei (module responsible for targeting) and loading with nitrofurazone (module responsible for therapeutic action) resulted in an effective delivery system that targets the surface of the parasites and shows trypanocidal activity.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhvFarsbvE&md5=82ebab64bd2d107e31bab214b4b543ec
24
Díaz-Rodríguez, A.; Davis, B. G. Curr. Opin. Chem. Biol. 2011, 15, 211
[ Crossref], [ PubMed], [ CAS], Google Scholar
24
Chemical modification in the creation of novel biocatalysts
Diaz-Rodriguez, Alba; Davis, Benjamin G.
Current Opinion in Chemical Biology (2011), 15 (2), 211-219CODEN: COCBF4; ISSN:1367-5931. (Elsevier B.V.)
A review. Enzymes are able to perform a multitude of chem. and biochem. transformations with efficiencies that are typically unrivaled by chem. catalysts. However, these evolved systems may lack breadth or utility in other non-natural applications. Altering enzyme and protein scaffolds through covalent modification can expand the usefulness of native biocatalysts not only for synthetic applications but also for therapeutic use. This review summarizes recent developments in the field of chem. modification of enzymes and how they can be applied to synthesis and biol. research.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXksFKnt70%253D&md5=330369b050ac09259dbe567b542b19b1
25
McGrath, N. A.; Andersen, K. A.; Davis, A. K. F.; Lomax, J. E.; Raines, R. T. Chem. Sci. 2015, 6, 752
[ Crossref], [ PubMed], [ CAS], Google Scholar
25
Diazo compounds for the bioreversible esterification of proteins
McGrath, Nicholas A.; Andersen, Kristen A.; Davis, Amy K. F.; Lomax, Jo E.; Raines, Ronald T.
Chemical Science (2015), 6 (1), 752-755CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)
A diazo compd. is shown to convert carboxylic acids to esters efficiently in an aq. environment. The basicity of the diazo compd. is crit.: low basicity does not lead to a reaction but high basicity leads to hydrolysis. This reactivity extends to carboxylic acid groups in a protein. The ensuing esters are hydrolyzed by human cellular esterases to regenerate protein carboxyl groups. This new mode of chem. modification could enable the key advantages of prodrugs to be translated from small-mols. to proteins.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhs1KnsL%252FM&md5=46fa03b7c0cdefd4a921117476799d17
26
(a) Kramer, J. R.; Deming, T. J. Biomacromolecules 2012, 13, 1719
[ ACS Full Text ], [ CAS], Google Scholar
26a
Preparation of Multifunctional and Multireactive Polypeptides via Methionine Alkylation
Kramer, Jessica R.; Deming, Timothy J.
Biomacromolecules (2012), 13 (6), 1719-1723CODEN: BOMAF6; ISSN:1525-7797. (American Chemical Society)
We report the development of a new "click"-type reaction for polypeptide modification based on the chemoselective alkylation of thioether groups in methionine residues. The controlled synthesis of methionine polymers and their alkylation by a broad range of functional reagents to yield stable sulfonium derivs. are described. These "methionine click" functionalizations are compatible with deprotection of other functional groups, use an inexpensive, natural amino acid that is readily polymd. and requires no protecting groups, and allow the introduction of a diverse range of functionality and reactive groups onto polypeptides.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XnsFOnsLw%253D&md5=952433a60f87eab5b8282739c587cf92
(b) Kramer, J. R.; Deming, T. J. Chem. Commun. 2013, 49, 5144
[ Crossref], [ PubMed], [ CAS], Google Scholar
26b
Reversible chemoselective tagging and functionalization of methionine containing peptides
Kramer, Jessica R.; Deming, Timothy J.
Chemical Communications (Cambridge, United Kingdom) (2013), 49 (45), 5144-5146CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
Reagents were developed to allow chemoselective tagging of methionine residues in peptides and polypeptides, subsequent bioorthogonal functionalization of the tags, and cleavage of the tags when desired. This methodol. can be used for triggered release of therapeutic peptides, or release of tagged protein digests from affinity columns.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXnsFarur0%253D&md5=5428bf5090a00b0e5667fec156c3ec5d
27
Tanaka, K.; Fukase, K.; Katsumura, S. Synlett 2011, 2011, 2115
[ Crossref], Google Scholar
There is no corresponding record for this reference.
28
Robinson, M. A.; Charlton, S. T.; Garnier, P.; Wang, X.-T.; Davis, S. S.; Perkins, A. C.; Frier, M.; Duncan, R.; Savage, T. J.; Wyatt, D. A.; Watson, S. A.; Davis, B. G. Proc. Natl. Acad. Sci. U. S. A. 2004, 101, 14527
[ Crossref], [ PubMed], [ CAS], Google Scholar
28
LEAPT: Lectin-directed enzyme-activated prodrug therapy
Robinson, Mark A.; Charlton, Stuart T.; Garnier, Philippe; Wang, Xiang-tao; Davis, Stanley S.; Perkins, Alan C.; Frier, Malcolm; Duncan, Ruth; Savage, Tony J.; Wyatt, David A.; Watson, Susan A.; Davis, Benjamin G.
Proceedings of the National Academy of Sciences of the United States of America (2004), 101 (40), 14527-14532CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)
Targeted drug delivery to selected sites allows reduced toxicity, enhanced efficiency and interchangeable target potential. We describe a bipartite drug-delivery system that exploits (i) endogenous carbohydrate-to-lectin binding to localize glycosylated enzyme conjugates to specific, predetd. cell types followed by (ii) administration of a prodrug activated by that predelivered enzyme at the desired site. The carbohydrate structure of an α-L-rhamnopyranosidase enzyme was specifically engineered through enzymic deglycosylation and chem. reglycosylation. Combined in vivo and in vitro techniques (gamma scintigraphy, microautoradiog. and confocal microscopy) detd. organ and cellular localization and demonstrated successful activation of α-L-rhamnopyranoside prodrug. Ligand competition expts. revealed enhanced, specific localization by endocytosis and a strongly carbohydrate-dependent, 60-fold increase in selectivity toward target cell hepatocytes that generated a >30-fold increase (from 0.02 to 0.66 mg) in protein delivered. Furthermore, glycosylation engineering enhanced the serum-uptake rate and enzyme stability. This created enzyme activity (0.2 units in hepatocytes) for prodrug therapy, the target of which was switched simply by sugar-type alteration. The therapeutic effectiveness of lectin-directed enzyme-activated prodrug therapy was shown through the construction of the prodrug of doxorubicin, Rha-DOX, and its application to reduce tumor burden in a hepatocellular carcinoma (HepG2) disease model.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXovVeru70%253D&md5=4d402206223fd1056fcde67391290c4d
29
Bavaro, T.; Filice, M.; Temporini, C.; Tengattini, S.; Serra, I.; Morelli, C. F.; Massolini, G.; Terreni, M. RSC Adv. 2014, 4, 56455
[ Crossref], [ CAS], Google Scholar
29
Chemoenzymatic synthesis of neoglycoproteins driven by the assessment of protein surface reactivity
Bavaro, T.; Filice, M.; Temporini, C.; Tengattini, S.; Serra, I.; Morelli, C. F.; Massolini, G.; Terreni, M.
RSC Advances (2014), 4 (99), 56455-56465CODEN: RSCACL; ISSN:2046-2069. (Royal Society of Chemistry)
In this paper a series of 2-iminomethoxyethyl mannose-based mono- and disaccharides have been synthesized by a chemoenzymic approach and used in coupling reactions with ε-amino groups of lysine residues in a model protein (RNase A, RNase A) to give semisynthetic neoglycoconjugates. In order to study the influence of structure of the glycans on the conjugation outcomes, an accurate characterization of the prepd. neoglycoproteins was performed by a combination of ESI-MS and LC-MS anal. methods. The analyses of the chymotryptic digests of the all neoglycoconjugates revealed six Lys-glycosylation sites with a the following order of lysine reactivity: Lys 1 » Lys 91 ≃ Lys 31 > Lys 61 ≃ Lys 66. A computational anal. of the reactivity of each lysine residue has been also carried out considering several parameters (amino acids surface exposure and pKa, protein flexibility). The in silico evaluation seems to confirm the order in lysine reactivity resulting from proteomic anal.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsl2gu7fE&md5=71e23551d12e603ca87faf2bfdcb21ba
30
Cal, P. M. S. D.; Vicente, J. B.; Pires, E.; Coelho, A. V.; Veiros, L. F.; Cordeiro, C.; Gois, P. M. P. J. Am. Chem. Soc. 2012, 134, 10299
[ ACS Full Text ], [ CAS], Google Scholar
30
Iminoboronates: A new strategy for reversible protein modification
Cal, Pedro M. S. D.; Vicente, Joao B.; Pires, Elisabete; Coelho, Ana V.; Veiros, Luis F.; Cordeiro, Carlos; Gois, Pedro M. P.
Journal of the American Chemical Society (2012), 134 (24), 10299-10305CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
Protein modification has entered the limelight of chem. and biol. sciences, since, by appending small mols. into proteins surfaces, fundamental biol. and biophys. processes may be studied and even modulated in a physiol. context. Herein the authors present a new strategy to modify the lysine's ε-amino group and the protein's N-terminal, based on the formation of stable iminoboronates in aq. media. This functionality enables the stable and complete modification of these amine groups, which can be reversible upon the addn. of fructose, dopamine, or glutathione. A detailed DFT study is also presented to rationalize the obsd. stability toward hydrolysis of the iminoboronate constructs.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XnsF2gurY%253D&md5=ad8e9263660d93401e1ccad61cd312db
31
Cal, P. M. S. D.; Frade, R. F. M.; Chudasama, V.; Cordeiro, C.; Caddick, S.; Gois, P. M. P. Chem. Commun. 2014, 50, 5261
[ Crossref], [ PubMed], [ CAS], Google Scholar
31
Targeting cancer cells with folic acid-iminoboronate fluorescent conjugates
Cal, Pedro M. S. D.; Frade, Raquel F. M.; Chudasama, Vijay; Cordeiro, Carlos; Caddick, Stephen; Gois, Pedro M. P.
Chemical Communications (Cambridge, United Kingdom) (2014), 50 (40), 5261-5263CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
Herein we present the synthesis of fluorescent 2-acetylbenzeneboronic acids that undergo B-N promoted conjugation with lysozyme and N-(2-aminoethyl) folic acid (EDA-FA), generating conjugates that are selectively recognized and internalized by cancer cells that over-express folic acid receptors.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXmsFequ7Y%253D&md5=dbd13397a6d6d33283e118e55ffb244c
32
Diethelm, S.; Schafroth, M. A.; Carreira, E. M. Org. Lett. 2014, 16, 3908
[ ACS Full Text ], [ CAS], Google Scholar
32
Amine-Selective Bioconjugation Using Arene Diazonium Salts
Diethelm, Stefan; Schafroth, Michael A.; Carreira, Erick M.
Organic Letters (2014), 16 (15), 3908-3911CODEN: ORLEF7; ISSN:1523-7052. (American Chemical Society)
A novel bioconjugation strategy is presented that relies on the coupling of diazonium terephthalates with amines in proteins. The diazonium captures the amine while the vicinal ester locks it through cyclization, ensuring no reversibility. The reaction is highly efficient and proceeds under mild conditions and short reaction times. Densely functionalized, complex natural products were directly coupled to proteins using low concns. of coupling partners.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtFCrtbfF&md5=91876c83f67d31189c501b567630900e
33
Chan, A. O.-Y.; Ho, C.-M.; Chong, H.-C.; Leung, Y.-C.; Huang, J.-S.; Wong, M.-K.; Che, C.-M. J. Am. Chem. Soc. 2012, 134, 2589
[ ACS Full Text ], [ CAS], Google Scholar
33
Modification of N-Terminal α-Amino Groups of Peptides and Proteins Using Ketenes
Chan, Anna On-Yee; Ho, Chi-Ming; Chong, Hiu-Chi; Leung, Yun-Chung; Huang, Jie-Sheng; Wong, Man-Kin; Che, Chi-Ming
Journal of the American Chemical Society (2012), 134 (5), 2589-2598CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
A method of highly selective N-terminal modification of proteins as well as peptides by an isolated ketene was developed. Modification of a library of unprotected peptides XSKFR (X varies over 20 natural amino acids) by an alkyne-functionalized ketene (I) at room temp. at pH 6.3 resulted in excellent N-terminal selectivity (modified α-amino group/modified ε-amino group = >99:1) for 13 out of the 20 peptides and moderate-to-high N-terminal selectivity (4:1 to 48:1) for 6 of the 7 remaining peptides. Using an alkyne-functionalized N-hydroxysuccinimide (NHS) ester (II) instead of I, the modification of peptides XSKFR gave internal lysine-modified peptides for 5 out of the 20 peptides and moderate-to-low N-terminal selectivity (5:1 to 1:4) for 13 out of the 20 peptides. Proteins including insulin, lysozyme, RNase A, and a therapeutic protein BCArg were selectively N-terminally modified at room temp. using ketene I, in contrast to the formation of significant or major amts. of di-, tri-, or tetra-modified proteins in the modification by NHS ester II. The I-modified proteins were further functionalized by a dansyl azide compd. through click chem. without the need for prior treatment.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhsVWisbg%253D&md5=af037a958d63180265aba0762ca77af7
34
(a) Kulkarni, C.; Kinzer-Ursem, T. L.; Tirrell, D. A. ChemBioChem 2013, 14, 1958
[ Crossref], [ PubMed], [ CAS], Google Scholar
34a
Selective Functionalization of the Protein N Terminus with N-Myristoyl Transferase for Bioconjugation in Cell Lysate
Kulkarni, Chethana; Kinzer-Ursem, Tamara L.; Tirrell, David A.
ChemBioChem (2013), 14 (15), 1958-1962CODEN: CBCHFX; ISSN:1439-4227. (Wiley-VCH Verlag GmbH & Co. KGaA)
This article describes the selective functionalization of the protein N terminus with N-myristoyl transferase for bioconjugation in cell lysate. NMT selectively labels engineered, non-natural substrate proteins in bacteria with a reactive, non-natural fatty acid. Quant. NMT-mediated labeling of engineered substrate proteins with reactive Myr analogs, as well as rapid and robust surface capture of labeled proteins to produce protein microarrays directly from cell lysate were reported.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhsVeisL7N&md5=ce54089c128b282c217a6b7330ad9338
(b) Wagner, A. M.; Fegley, M. W.; Warner, J. B.; Grindley, C. L. J.; Marotta, N. P.; Petersson, E. J. J. Am. Chem. Soc. 2011, 133, 15139
[ ACS Full Text ], [ CAS], Google Scholar
34b
N-Terminal Protein Modification Using Simple Aminoacyl Transferase Substrates
Wagner, Anne M.; Fegley, Mark W.; Warner, John B.; Grindley, Christina L. J.; Marotta, Nicholas P.; Petersson, E. James
Journal of the American Chemical Society (2011), 133 (38), 15139-15147CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
Methods for synthetically manipulating protein structure enable greater flexibility in the study of protein function. Previous characterization of the Escherichia coli aminoacyl tRNA transferase (AaT) has shown that it can modify the N-terminus of a protein with an amino acid from a tRNA or a synthetic oligonucleotide donor. Here, it is demonstrated that AaT can efficiently use a minimal adenosine substrate, which can be synthesized in one to two steps from readily available starting materials. The enzymic activity of AaT was characterized with aminoacyl adenosyl donors and it was found that reaction products do not inhibit AaT. The use of adenosyl donors removes the substrate limitations imposed by the use of synthetases for tRNA charging and avoids the complex synthesis of an oligonucleotide donor. Thus, these AaT donors increase the potential substrate scope and reaction scale for N-terminal protein modification under conditions that maintain folding.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhtFaks7rI&md5=09ad42b27993fa2817c220962c17fb1a
35
(a) Schlick, T. L.; Ding, Z.; Kovacs, E. W.; Francis, M. B. J. Am. Chem. Soc. 2005, 127, 3718
[ ACS Full Text ], [ CAS], Google Scholar
35a
Dual-surface modification of the Tobacco mosaic virus
Schlick, Tara L.; Ding, Zhebo; Kovacs, Ernest W.; Francis, Matthew B.
Journal of the American Chemical Society (2005), 127 (11), 3718-3723CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
The protein shell of the tobacco mosaic virus (TMV) provides a robust and practical tubelike scaffold for the prepn. of nanoscale materials. To expand the range of applications for which the capsid can be used, two synthetic strategies have been developed for the attachment of new functionality to either the exterior or the interior surface of the virus. The first of these is accomplished using a highly efficient diazonium coupling/oxime formation sequence, which installs >2000 copies of a material component on the capsid exterior. Alternatively, the inner cavity of the tube can be modified by attaching amines to glutamic acid side chains through a carbodiimide coupling reaction. Both of these reactions have been demonstrated for a series of substrates, including biotin, chromophores, and crown ethers. Through the attachment of PEG polymers to the capsid exterior, org.-sol. TMV rods have been prepd. Finally, the orthogonality of these reactions has been demonstrated by installing different functional groups on the exterior and interior surfaces of the same capsid assemblies.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXhs1ant7w%253D&md5=417dfb81edc43b89ef121f8c67ed653a
(b) Hooker, J. M.; Kovacs, E. W.; Francis, M. B. J. Am. Chem. Soc. 2004, 126, 3718
[ ACS Full Text ], [ CAS], Google Scholar
35b
Interior surface modification of bacteriophage MS2
Hooker, Jacob M.; Kovacs, Ernest W.; Francis, Matthew B.
Journal of the American Chemical Society (2004), 126 (12), 3718-3719CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
An efficient strategy for the interior surface functionalization of MS2 viral capsids is reported, featuring a new hetero-Diels-Alder bioconjugation reaction. After virus isolation, the RNA genome was removed from the spherical particles by exposure to pH 11.8 conditions for a period of 4 h. Following this, 180 tyrosine residues on the interior surface of each "empty" capsid shell were modified by using a site-selective diazonium-coupling reaction. To attach addnl. functionality, the azo conjugate was reduced with Na2S2O4 to afford an ortho-amino tyrosine deriv. Oxidn. of this moiety with NaIO4 produced an o-iminoquinone on the protein surface, which was found to undergo an efficient hetero-Diels-Alder reaction with N-(4-aminophenyl)acrylamide. This 4-step procedure can be carried out in under 4 h, reaches high levels of conversion, and yields the desired conjugates in >60% overall yield.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXhvVyqu7o%253D&md5=278140e9122ec58334673c6415d3ed1b
36
Gavrilyuk, J.; Ban, H.; Nagano, M.; Hakamata, W.; Barbas, C. F. Bioconjugate Chem. 2012, 23, 2321
[ ACS Full Text ], [ CAS], Google Scholar
36
Formylbenzene Diazonium Hexafluorophosphate Reagent for Tyrosine-Selective Modification of Proteins and the Introduction of a Bioorthogonal Aldehyde
Gavrilyuk, Julia; Ban, Hitoshi; Nagano, Masanobu; Hakamata, Wataru; Barbas, Carlos F.
Bioconjugate Chemistry (2012), 23 (12), 2321-2328CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
4-Formylbenzene diazonium hexafluorophosphate (FBDP) is a novel bench-stable cryst. diazonium salt that reacts selectively with tyrosine to install a bioorthogonal aldehyde functionality. Model studies with N-acyl-tyrosine methylamide allowed the authors to identify conditions optimal for tyrosine ligation reactions with small peptides and proteins. FBDP-based conjugation was used for the facile introduction of small mol. tags, poly(ethylene glycol) chains (PEGylation), and functional small mols. onto model proteins and to label the surface of living cells.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xhslemu7vP&md5=65b3af53d0d71681ded8c108ba2054aa
37
Zhang, J.; Ma, D.; Du, D.; Xi, Z.; Yi, L. Org. Biomol. Chem. 2014, 12, 9528
[ Crossref], [ PubMed], [ CAS], Google Scholar
37
An efficient reagent for covalent introduction of alkynes into proteins
Zhang, Jie; Ma, Dejun; Du, Dawei; Xi, Zhen; Yi, Long
Organic & Biomolecular Chemistry (2014), 12 (47), 9528-9531CODEN: OBCRAK; ISSN:1477-0520. (Royal Society of Chemistry)
A cheap and bench-stable reagent was synthesized for direct and covalent introduction of alkynes into tyrosine of target proteins, which can be further modified based on Click reaction to achieve fluorescence labeling or PEGylation. This reagent should be a generally useful toolbox for chem. biol. and biomaterials.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhslKrsbrL&md5=9b70cd50737258a4898f180fa6f9a4b0
38
Chen, S.; Tsao, M.-L. Bioconjugate Chem. 2013, 24, 1645
[ ACS Full Text ], [ CAS], Google Scholar
38
Genetic Incorporation of a 2-Naphthol Group into Proteins for Site-Specific Azo Coupling
Chen, Shuo; Tsao, Meng-Lin
Bioconjugate Chemistry (2013), 24 (10), 1645-1649CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
The 2-naphthol analog of tyrosine, 2-amino-3-(6-hydroxy-2-naphthyl)-propanoic acid (NpOH), has been genetically introduced into proteins in Escherichia coli. This is achieved through the directed evolution of orthogonal aminoacyl-tRNA synthetase/tRNA pairs that selectively charge the target amino acid in response to the amber stop codon, UAG. Moreover, chemoselective azo coupling reactions have been revealed between the 2-naphthol group and diazotized aniline derivs. that are substituted with an electron donating moiety. The coupling reactions required a very mild condition (pH 7) with great reaction rate (less than 2 h at 0 °C), high efficiency, and excellent selectivity.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhsFehu7zE&md5=a0f72083e99920da221eddbf7bff198f
39
(a) Lorenzi, M.; Puppo, C.; Lebrun, R.; Lignon, S.; Roubaud, V.; Martinho, M.; Mileo, E.; Tordo, P.; Marque, S. R. A.; Gontero, B.; Guigliarelli, B.; Belle, V. Angew. Chem., Int. Ed. 2011, 50, 9108
[ Crossref], [ PubMed], [ CAS], Google Scholar
39a
Tyrosine-Targeted Spin Labeling and EPR Spectroscopy: An Alternative Strategy for Studying Structural Transitions in Proteins
Lorenzi, Magali; Puppo, Carine; Lebrun, Regine; Lignon, Sabrina; Roubaud, Valerie; Martinho, Marlene; Mileo, Elisabetta; Tordo, Paul; Marque, Sylvain R. A.; Gontero, Brigitte; Guigliarelli, Bruno; Belle, Valerie
Angewandte Chemie, International Edition (2011), 50 (39), 9108-9111, S9108/1-S9108/9CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
The authors present the selective grafting of a nitroxide probe to tyrosine by using, the Mannich-type reaction on CP12, a protein bearing only one natural tyrosine residue. This unique tyrosine residue, located at position 78 in the sequence of a total of 80 amino acids, makes this protein an ideal candidate for demonstrating the feasibility of tyrosine-targeted spin labeling.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhtVOmsrjE&md5=5495a295b0609aa25af8d2b900f1aeab
(b) McFarland, J. M.; Joshi, N. S.; Francis, M. B. J. Am. Chem. Soc. 2008, 130, 7639
[ ACS Full Text ], [ CAS], Google Scholar
39b
Characterization of a Three-Component Coupling Reaction on Proteins by Isotopic Labeling and Nuclear Magnetic Resonance Spectroscopy
McFarland, Jesse M.; Joshi, Neel S.; Francis, Matthew B.
Journal of the American Chemical Society (2008), 130 (24), 7639-7644CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
A three-component Mannich-type electrophilic arom. substitution reaction was previously developed to target the phenolic side chain of tyrosine residues on proteins. This reaction proceeds under mild conditions and provides a convenient alternative to lysine-targeting strategies. However, the use of reactive aldehydes, such as formaldehyde, warrants careful inspection of the reaction products to ensure that other modifications have not occurred. Through the use of isotopically enriched reagents, NMR-based studies were used to obtain structural confirmation of the tyrosine-modification products. These expts. also revealed the formation of a reaction byproduct arising from the indole ring of tryptophan residues. Cysteine residues were shown to not participate in the reaction, except in the case of a reduced disulfide, which formed a dithioacetal. The authors anticipate that this anal. method will prove useful for the detailed study of a no. of bioconjugation reactions.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXmtlWnur8%253D&md5=bb7ca7ed789e3e447e7de7dac5c54941
(c) Romanini, D. W.; Francis, M. B. Bioconjugate Chem. 2008, 19, 153
[ ACS Full Text ], [ CAS], Google Scholar
39c
Attachment of Peptide Building Blocks to Proteins Through Tyrosine Bioconjugation
Romanini, Dante W.; Francis, Matthew B.
Bioconjugate Chemistry (2008), 19 (1), 153-157CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
Recent efforts have yielded a no. of short peptide sequences with useful binding, sensing, and cellular uptake properties. To attach these sequences to tyrosine residues on intact proteins, a three-component Mannich-type strategy is reported. Two solid phase synthetic routes were developed to access peptides up to 20 residues in length with anilines at either the N- or C-termini. In the presence of 20 mM formaldehyde, these functional groups were coupled to tyrosine residues on proteins under mild reaction conditions. The identities of the resulting bioconjugates were confirmed using mass spectrometry and immunoblot anal. Screening expts. have demonstrated that the method is compatible with substrates contg. all of the amino acids, including lysine and cysteine residues. Importantly, tyrosine residues on proteins exhibit much faster reaction rates, allowing short peptides contg. this residue to be coupled without cross reactions.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXhsVWgtbbF&md5=e66a855c3a122ae3ea53db9e7d0c9be3
(d) Joshi, N. S.; Whitaker, L. R.; Francis, M. B. J. Am. Chem. Soc. 2004, 126, 15942
[ ACS Full Text ], [ CAS], Google Scholar
39d
A Three-Component Mannich-Type Reaction for Selective Tyrosine Bioconjugation
Joshi, Neel S.; Whitaker, Leanna R.; Francis, Matthew B.
Journal of the American Chemical Society (2004), 126 (49), 15942-15943CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
A new selective bioconjugation reaction is described for the modification of tyrosine residues on protein substrates. The reaction uses imines formed in situ from aldehydes and electron-rich anilines to modify phenolic side chains through a Mannich-type electrophilic arom. substitution pathway. The reaction takes place under mild pH and temp. conditions and can modify protein substrates at concns. as low as 20 μM. Using an efficient fluorescence-based assay, we demonstrated the reaction using a no. of aldehydes and protein targets. Importantly, proteins lacking surface-accessible tyrosines remained unmodified. It was also demonstrated that enzymic activity is preserved under the mild reaction conditions. This strategy represents one of the first carbon-carbon bond-forming reactions for protein modification and provides an important complement to more commonly used lysine- and cysteine-based methods.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXpvFWjur8%253D&md5=d9cb096caf0ad9046b42c8e6bdb7145a
40
Mileo, E.; Etienne, E.; Martinho, M.; Lebrun, R.; Roubaud, V.; Tordo, P.; Gontero, B.; Guigliarelli, B.; Marque, S. R. A.; Belle, V. Bioconjugate Chem. 2013, 24, 1110
[ ACS Full Text ], [ CAS], Google Scholar
40
Enlarging the Panoply of Site-Directed Spin Labeling Electron Paramagnetic Resonance (SDSL-EPR): Sensitive and Selective Spin-Labeling of Tyrosine Using an Isoindoline-Based Nitroxide
Mileo, Elisabetta; Etienne, Emilien; Martinho, Marlene; Lebrun, Regine; Roubaud, Valerie; Tordo, Paul; Gontero, Brigitte; Guigliarelli, Bruno; Marque, Sylvain R. A.; Belle, Valerie
Bioconjugate Chemistry (2013), 24 (6), 1110-1117CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
Site-directed spin labeling (SDSL) combined with EPR spectroscopy has emerged as a powerful approach to study structure and dynamics in proteins. One limitation of this approach is the fact that classical spin labels are functionalized to be grafted on natural or site-directed mutagenesis generated cysteine residues. Despite the widespread success of cysteine-based modification strategies, the technique becomes unsuitable when cysteine residues play a functional or structural role in the protein under study. To overcome this limitation, the authors propose an isoindoline-based nitroxide to selectively target tyrosine residues using a Mannich type reaction, the feasibility of which has been demonstrated in a previous study. This nitroxide has been synthesized and successfully grafted successively on p-cresol, a small tetrapeptide and a model protein: a small chloroplastic protein CP12 having functional cysteines and a single tyrosine. Studying the assocn. of the labeled CP12 with its partner protein, the isoindoline-based nitroxide is a good reporter to reveal changes in its local environment contrary to the previous study where the label was poorly sensitive to probe structural changes. The successful targeting of tyrosine residues with the isoindoline-based nitroxide thus offers a highly promising approach, complementary to the classical cysteine-SDSL one, which significantly enlarges the field of applications of the technique for probing protein dynamics.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXmvFyqs7s%253D&md5=c6e154a7f0c42f5dad4b167afb3c371a
41
Guo, H.-M.; Minakawa, M.; Ueno, L.; Tanaka, F. Bioorg. Med. Chem. Lett. 2009, 19, 1210
[ Crossref], [ PubMed], [ CAS], Google Scholar
41
Synthesis and evaluation of a cyclic imine derivative conjugated to a fluorescent molecule for labeling of proteins
Guo, Hai-Ming; Minakawa, Maki; Ueno, Lynn; Tanaka, Fujie
Bioorganic & Medicinal Chemistry Letters (2009), 19 (4), 1210-1213CODEN: BMCLE8; ISSN:0960-894X. (Elsevier B.V.)
A cyclic imine conjugated to a fluorescent dansyl group was synthesized and used for covalent labeling of proteins. The covalent attachment to proteins was confirmed by gel electrophoresis and mass anal.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXit1Wrurw%253D&md5=89f3027f9c158ec07d41199bed05b0ed
42
Ban, H.; Gavrilyuk, J.; Barbas, C. F. J. Am. Chem. Soc. 2010, 132, 1523
[ ACS Full Text ], [ CAS], Google Scholar
42
Tyrosine bioconjugation through aqueous ene-type reactions: A click-like reaction for tyrosine
Ban, Hitoshi; Gavrilyuk, Julia; Barbas, Carlos F.
Journal of the American Chemical Society (2010), 132 (5), 1523-1525CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
A new and versatile class of cyclic diazodicarboxamides that reacts efficiently and selectively with phenols and the phenolic side chain of tyrosine through an ene-like reaction is reported. This mild aq. tyrosine ligation reaction works over a broad pH range and expands the repertoire of aq. chemistries available for small mol., peptide, and protein modification. The tyrosine ligation reactions are shown to be compatible with the labeling of native enzymes and antibodies in a buffered aq. soln. This reaction provides a novel synthetic approach to bispecific antibodies. The authors believe this reaction will find broad utility in peptide and protein chem. and in the chem. of phenol-contg. compds.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXkt1Wrug%253D%253D&md5=876ee34e149ceed4f70f7fd4efbb25ba
43
(a) Hu, Q.-Y.; Allan, M.; Adamo, R.; Quinn, D.; Zhai, H.; Wu, G.; Clark, K.; Zhou, J.; Ortiz, S.; Wang, B.; Danieli, E.; Crotti, S.; Tontini, M.; Brogioni, G.; Berti, F. Chem. Sci. 2013, 4, 3827
[ Crossref], [ CAS], Google Scholar
43a
Synthesis of a well-defined glycoconjugate vaccine by a tyrosine-selective conjugation strategy
Hu, Qi-Ying; Allan, Martin; Adamo, Roberto; Quinn, Doug; Zhai, Huili; Wu, Guangxiang; Clark, Kirk; Zhou, Jing; Ortiz, Sonia; Wang, Bing; Danieli, Elisa; Crotti, Stefano; Tontini, Marta; Brogioni, Giulia; Berti, Francesco
Chemical Science (2013), 4 (10), 3827-3832CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)
An anti-candidiasis glycoconjugate vaccine was prepd. via a tyrosine-selective alkynylation and a click chem. mediated glycoconjugation sequence. It features a well-defined glycan, protein carrier, and connectivity. The construct, although with significantly lower carbohydrate loading and a shorter β-(1,3) glucan chain than the well-established anti-candidiasis vaccine derived from the random conjugation of laminarin at lysines, elicited a comparable level of specific IgG antibodies.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtlentrnP&md5=ff8226bd1851cd36db4d672ac93edf39
(b) Adamo, R.; Hu, Q.-Y.; Torosantucci, A.; Crotti, S.; Brogioni, G.; Allan, M.; Chiani, P.; Bromuro, C.; Quinn, D.; Tontini, M.; Berti, F. Chem. Sci. 2014, 5, 4302
[ Crossref], [ CAS], Google Scholar
43b
Deciphering the structure-immunogenicity relationship of anti-Candida glycoconjugate vaccines
Adamo, Roberto; Hu, Qi-Ying; Torosantucci, Antonella; Crotti, Stefano; Brogioni, Giulia; Allan, Martin; Chiani, Paola; Bromuro, Carla; Quinn, Douglas; Tontini, Marta; Berti, Francesco
Chemical Science (2014), 5 (11), 4302-4311CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)
The elucidation of the mol. details underlying the immune properties of glycoconjugate vaccines has largely focused on the carbohydrate moiety, while very little is known on the effect of the corresponding conjugation sites. Herein we constructed a set of β-(1 → 3) glucan oligosaccharide conjugates with a well-defined glycan structure, connected to patterns of predetd. tyrosine or lysine residues onto the CRM197 carrier protein. To evaluate the effect of multivalent architecture in the glycan presentation, a novel linker enabling tyrosine-directed ligation of couples of oligosaccharides was prepd. The potential of these constructs as anti-Candida vaccines was evaluated in vivo, using as controls glycoconjugates prepd. by a conventional random coupling strategy, and the structure-immune properties relationship was established. We found that: (i) the tyrosine-directed ligation resulted in higher anti-glycan IgG levels in comparison to the conjugation at predetd. lysine residues; (ii) the presentation of the carbohydrate antigen with a biantennary cluster of glycans onto specific tyrosine residues did not further increase the anti-glycan antibody level; (iii) the sera deriving from immunization with defined conjugates at tyrosine and, particularly at lysine residues, were proven stronger inhibitors of fungal adhesion to human epithelial cells in comparison to those from conjugates prepd. by classic random chem.; (iv) the presence of antibodies directed to the linkers did not affect the anti-glycan immune response. These findings suggest that a careful choice of the defined sites of conjugation and the loading d. of antigens are important factors to raise high-quality anti-carbohydrate antibodies.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtFSgs7fF&md5=6c6469c55d8a2020eb7ad1d424f78525
(c) Nilo, A.; Allan, M.; Brogioni, B.; Proietti, D.; Cattaneo, V.; Crotti, S.; Sokup, S.; Zhai, H.; Margarit, I.; Berti, F.; Hu, Q.-Y.; Adamo, R. Bioconjugate Chem. 2014, 25, 2105
[ ACS Full Text ], [ CAS], Google Scholar
43c
Tyrosine-Directed Conjugation of Large Glycans to Proteins via Copper-Free Click Chemistry
Nilo, Alberto; Allan, Martin; Brogioni, Barbara; Proietti, Daniela; Cattaneo, Vittorio; Crotti, Stefano; Sokup, Samantha; Zhai, Huili; Margarit, Immaculada; Berti, Francesco; Hu, Qi-Ying; Adamo, Roberto
Bioconjugate Chemistry (2014), 25 (12), 2105-2111CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
The insertion of alkyne-contg. bifunctional linkers into the tyrosine residues of the carrier protein, followed by the copper mediated azide-alkyne [3 + 2] cycloaddn. of carbohydrates, is a robust approach for the prepn. of glycoconjugates with defined glycans, carrier, and connectivity. Conjugation of Group B Streptococcus (GBS) capsular polysaccharides to streptococcal pilus protein could extend the vaccine coverage to a variety of strains. Application of the authors' protocol to these large charged polysaccharides occurred at low yields. Herein the authors developed a tyrosine-directed conjugation approach based on the copper-free click chem. of sugars modified with cyclooctynes, which enables efficient condensation of synthetic carbohydrates. Most importantly, this strategy is more effective than the corresponding copper catalyzed reaction for the insertion of GBS onto the tyrosine residues of GBS pilus proteins, previously selected as vaccine antigens through the so-called reverse vaccinol. Integrity of protein epitopes in the modified proteins was ascertained by competitive ELISA, and conjugation of polysaccharide to protein was confirmed by SDS page electrophoresis and immunoblot assays. The amt. of conjugated polysaccharide was estd. by high-performance anion-exchange chromatog. coupled with pulsed amperometric detection (HPAEC-PAD). The described technol. is particularly suitable for proteins used with the dual role of vaccine antigen and carrier for the carbohydrate haptens.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhvFGku7zI&md5=7e62afdb0e1d506b664dc101af627c9c
44
Bauer, D. M.; Ahmed, I.; Vigovskaya, A.; Fruk, L. Bioconjugate Chem. 2013, 24, 1094
[ ACS Full Text ], [ CAS], Google Scholar
44
Clickable Tyrosine Binding Bifunctional Linkers for Preparation of DNA-Protein Conjugates
Bauer, Dennis M.; Ahmed, Ishtiaq; Vigovskaya, Antonina; Fruk, Ljiljana
Bioconjugate Chemistry (2013), 24 (6), 1094-1101CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
The authors prepd. bifunctional linkers contg. clickable functional groups that enable prepn. of protein-DNA conjugates through binding onto tyrosine residues. Mild conjugation strategy was demonstrated using two proteins, streptavidin (STV) and myoglobin (Mb) and it resulted in conjugates with preserved functionality of both the proteins and DNA strands. Furthermore, protein-DNA conjugates can be successfully immobilized onto solid surface contg. complementary DNA strands and the enzymic activity of Mb-DNA conjugates is even higher than that of corresponding conjugates prepd. through Lys binding.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXot1Glur0%253D&md5=ea7c9c67e6330be49e61e71fc29fd550
45
Chalker, J. M.; Bernardes, G. J. L.; Davis, B. G. Acc. Chem. Res. 2011, 44, 730
[ ACS Full Text ], [ CAS], Google Scholar
45
A "Tag-and-Modify" Approach to Site-Selective Protein Modification
Chalker, Justin M.; Bernardes, Goncalo J. L.; Davis, Benjamin G.
Accounts of Chemical Research (2011), 44 (9), 730-741CODEN: ACHRE4; ISSN:0001-4842. (American Chemical Society)
A review. Covalent modification can expand a protein's functional capacity. Fluorescent or radioactive labeling, for instance, allows imaging of a protein in real time. Labeling with an affinity probe enables isolation of target proteins and other interacting mols. At the other end of this functional spectrum, protein structures can be naturally altered by enzymic action. Protein-protein interactions, genetic regulation, and a range of cellular processes are under the purview of these post-translational modifications. The ability of protein chemists to install these covalent addns. selectively has been crit. for elucidating their roles in biol. Frequently the transformations must be applied in a site-specific manner, which demands the most selective chem. In this Account, we discuss the development and application of such chem. in our lab. A centerpiece of our strategy is a "tag-and-modify" approach, which entails sequential installation of a uniquely reactive chem. group into the protein (the "tag") and the selective or specific modification of this group. The chem. tag can be a natural or unnatural amino acid residue. Of the natural residues, cysteine is the most widely used as a tag. Early work in our program focused on selective disulfide formation in the synthesis of glycoproteins. For certain applications, the susceptibility of disulfides to redn. was a limitation and prompted the development of several methods for the synthesis of more stable thioether modifications. The desulfurization of disulfides and conjugate addn. to dehydroalanine are two routes to these modifications. The dehydroalanine tag has since proven useful as a general precursor to many modifications after conjugate addn. of various nucleophiles; phosphorylated, glycosylated, peptidylated, prenylated, and even mimics of methylated and acetylated lysine-contg. proteins are all accessible from dehydroalanine. While cysteine is a useful tag for selective modification, unnatural residues present the opportunity for bio-orthogonal chem. Azide-, arylhalide-, alkyne-, and alkene-contg. amino acids can be incorporated into proteins genetically and can be specifically modified through various transformations. These transformations often rely on metal catalysis. The Cu-catalyzed azide-alkyne addn., Ru-catalyzed olefin metathesis, and Pd-catalyzed cross-coupling are examples of such transformations. In the course of adapting these reactions to protein modification, we learned much about the behavior of these reactions in water, and in some cases entirely new catalysts were developed. Through a combination of these bio-orthogonal transformations from the panel of tag-and-modify reactions, multiple and distinct modifications can be installed on protein surfaces. Multiple modifications are common in natural systems, and synthetic access to these proteins has enabled study of their biol. role. Throughout these investigations, much has been learned in chem. and biol. The demands of selective protein modification have revealed many aspects of reaction mechanisms, which in turn have guided the design of reagents and catalysts that allow their successful deployment in water and in biol. milieu. With this ability to modify proteins, it is now possible to interrogate biol. systems with precision that was not previously possible.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXlvFCmtb8%253D&md5=6dc1df95902cb75e3f190f6721e621e1
46
Boutureira, O.; Bernardes, G. J. L.; Fernández-González, M.; Anthony, D. C.; Davis, B. G. Angew. Chem., Int. Ed. 2012, 51, 1432
[ Crossref], [ PubMed], [ CAS], Google Scholar
46
Selenenylsulfide-linked Homogeneous Glycopeptides and Glycoproteins: Synthesis of Human "Hepatic Se Metabolite A"
Boutureira, Omar; Bernardes, Goncalo J. L.; Fernandez-Gonzalez, Marta; Anthony, Daniel C.; Davis, Benjamin G.
Angewandte Chemie, International Edition (2012), 51 (6), 1432-1436, S1432/1-S1432/46CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
The authors present the synthesis of selenenylsulfide-linked (glycosyl-SeS-Cys) glycopeptides and glycoproteins using a Cys-specific selenylation protocol of cysteine moiety in peptides and proteins, resp. The first synthesis and full characterization of human hepatic Se metabolite A, 5, is also reported.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XitVegsw%253D%253D&md5=2d183abedd5298ab09420005485ecf1c
47
(a) Chalker, J. M.; Gunnoo, S. B.; Boutureira, O.; Gerstberger, S. C.; Fernández-González, M.; Bernardes, G. J. L.; Griffin, L.; Hailu, H.; Schofield, C. J.; Davis, B. G. Chem. Sci. 2011, 2, 1666
[ Crossref], [ CAS], Google Scholar
47a
Methods for converting cysteine to dehydroalanine on peptides and proteins
Chalker, Justin M.; Gunnoo, Smita B.; Boutureira, Omar; Gerstberger, Stefanie C.; Fernandez-Gonzalez, Marta; Bernardes, Goncalo J. L.; Griffin, Laura; Hailu, Hanna; Schofield, Christopher J.; Davis, Benjamin G.
Chemical Science (2011), 2 (9), 1666-1676CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)
Dehydroalanine is a synthetic precursor to a wide array of protein modifications. We describe multiple methods for the chem. conversion of cysteine to dehydroalanine on peptides and proteins. The scope and limitations of these methods were investigated with attention paid to side reactions, scale, and aq.- and bio-compatibility. The most general method investigated-a bis-alkylation-elimination of cysteine to dehydroalanine-was applied successfully to multiple proteins and enabled the site-selective synthesis of a glycosylated antibody.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXpvFCms74%253D&md5=58e4b225561dc8cc2a6248bb31cd4758
(b) Bernardes, G. J. L.; Chalker, J. M.; Errey, J. C.; Davis, B. G. J. Am. Chem. Soc. 2008, 130, 5052
[ ACS Full Text ], [ CAS], Google Scholar
47b
Facile Conversion of Cysteine and Alkyl Cysteines to Dehydroalanine on Protein Surfaces: Versatile and Switchable Access to Functionalized Proteins
Bernardes, Goncalo J. L.; Chalker, Justin M.; Errey, James C.; Davis, Benjamin G.
Journal of the American Chemical Society (2008), 130 (15), 5052-5053CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
An efficient and robust oxidative elimination of cysteine to dehydroalanine has been discovered. The reaction is induced by O-mesitylenesulfonylhydroxylamine (MSH) and is compatible with methionine. The key elimination has been executed on protein surfaces and allows ready access to different post-translationally modified proteins through conjugate addn. of sulfur nucleophiles to dehydroalanine. Treatment of the resulting thioether with MSH results in regeneration of dehydroalanine, allowing a "functional switch" by subsequent addn. of a different thiol.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXjslahur8%253D&md5=94379dc2edaed8511e00098c6f89fac9
(c) Bernardes, G. J. L.; Grayson, E. J.; Thompson, S.; Chalker, J. M.; Errey, J. C.; Oualid, F. E.; Claridge, T. D. W.; Davis, B. G. Angew. Chem., Int. Ed. 2008, 47, 2244
[ Crossref], [ PubMed], [ CAS], Google Scholar
47c
From disulfide- to thioether-linked glycoproteins
Bernardes, Goncalo J. L.; Grayson, Elizabeth J.; Thompson, Sam; Chalker, Justin M.; Errey, James C.; ElOualid, Farid; Claridge, Timothy D. W.; Davis, Benjamin G.
Angewandte Chemie, International Edition (2008), 47 (12), 2244-2247CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
The introduction of a thiol tag in combination with chemoselective ligation to form a disulfide-linked bioconjugate is a selective and useful method for site-selective protein glycosylation. The phosphine-mediated desulfurization of such glycoconjugates to their reductant-resistant thioether-linked counterparts completes a convergent, site-selective synthesis of thioether-linked glycoproteins.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXktV2rt74%253D&md5=ba3211b263edd152d3e5ac348ec84c06
48
Haj-Yahya, N.; Hemantha, H. P.; Meledin, R.; Bondalapati, S.; Seenaiah, M.; Brik, A. Org. Lett. 2014, 16, 540
[ ACS Full Text ], [ CAS], Google Scholar
48
Dehydroalanine-Based Diubiquitin Activity Probes
Haj-Yahya, Najat; Hemantha, Hosahalli P.; Meledin, Roman; Bondalapati, Somasekhar; Seenaiah, Mallikanti; Brik, Ashraf
Organic Letters (2014), 16 (2), 540-543CODEN: ORLEF7; ISSN:1523-7052. (American Chemical Society)
A strategy for the synthesis of dehydroalanine based diubiquitin activity probes is described. The site-specific introduction of dehydroalanine was achieved from diubiquitin bearing Cys residue near the scissile bond between two ubiquitins linked through Lys48, Lys63 or in a head to tail fashion. The probes were characterized for their activities with various deubiquitinases, which open new opportunities in studying deubiquitinases in various settings.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhvFymsb7M&md5=62fad59df71f0444388efbe310aaca72
49
Boutureira, O.; Bernardes, G. J. L.; D’Hooge, F.; Davis, B. G. Chem. Commun. 2011, 47, 10010
[ Crossref], [ PubMed], [ CAS], Google Scholar
49
Direct radiolabelling of proteins at cysteine using [18F]-fluorosugars
Boutureira, Omar; Bernardes, Goncalo J. L.; D'Hooge, Francois; Davis, Benjamin G.
Chemical Communications (Cambridge, United Kingdom) (2011), 47 (36), 10010-10012CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
A strategy for the site-specific attachment of 2-deoxy-2-fluorosugars to cysteine and dehydroalanine tagged proteins is reported. When combined with thionation of fluorosugars, such as the widely available 18F probe 2-deoxy-2-[18F]fluoroglucose ([18F]FDG), this methodol. allows fast and direct access to site-specific [18F]FDG-labeled proteins.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhtV2htrrK&md5=1e4e04570c0d0df64792885d1e85b5d5
50
Kunstelj, M.; Fidler, K.; Škrajnar, Š.; Kenig, M.; Smilović, V.; Kusterle, M.; Caserman, S.; Zore, I.; Porekar, V. G.; Jevševar, S. Bioconjugate Chem. 2013, 24, 889
[ ACS Full Text ], [ CAS], Google Scholar
50
Cysteine-Specific PEGylation of rhG-CSF via Selenylsulfide Bond
Kunstelj, Menci; Fidler, Katarina; Skrajnar, Spela; Kenig, Maja; Smilovic, Vanja; Kusterle, Mateja; Caserman, Simon; Zore, Irena; Porekar, Vladka Gaberc; Jevsevar, Simona
Bioconjugate Chemistry (2013), 24 (6), 889-896CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
A new PEGylation reagent enabling selective modification of free thiol groups is described in this article. The reagent was synthesized by attaching linear polyethylene glycol (PEG) N-hydroxysuccinimide to selenocystamine. The reaction was very fast, resulting in over 95% conversion yield. The active group of this new PEG-Se reagent is a diselenide, reacting with thiols via thiol/diselenide exchange reaction. Recombinant human granulocyte colony-stimulating factor (rhG-CSF) with an unpaired cysteine at the position 18 (Cys18) was used as a model protein. It was comparatively PEGylated with the new PEG-Se reagent, as well as with com. available maleimide (PEG-Mal) and ortho-pyridyl disulfide (PEG-OPSS) PEG reagents. The highest PEGylation yield was obtained with PEG-Mal, followed by PEG-OPSS and PEG-Se. The reaction rates of PEG-Mal and PEG-Se were comparable, while the reaction rate of PEG-OPSS was lower. Purified monoPEGylated rhG-CSF conjugates were characterized and compared. Differences in activity, stability, and in vivo performance were obsd., although all conjugates contained a 20 kDa PEG attached to the Cys18. Minor conformational changes were obsd. in the conjugate prepd. with PEG-Mal. These changes were also reflected in low in vitro biol. activity and aggregate formation of the maleimide conjugate. The conjugate prepd. with PEG-Se had the highest in vitro biol. activity, while the conjugate prepd. with PEG-OPSS had the best in vivo performance.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXmt1ylt70%253D&md5=e753b238a06104579e8819367cd65919
51
Grayson, E. J.; Bernardes, G. J. L.; Chalker, J. M.; Boutureira, O.; Koeppe, J. R.; Davis, B. G. Angew. Chem., Int. Ed. 2011, 50, 4127
[ Crossref], [ PubMed], [ CAS], Google Scholar
51
A Coordinated Synthesis and Conjugation Strategy for the Preparation of Homogeneous Glycoconjugate Vaccine Candidates
Grayson, Elizabeth J.; Bernardes, Goncalo J. L.; Chalker, Justin M.; Boutureira, Omar; Koeppe, Julia R.; Davis, Benjamin G.
Angewandte Chemie, International Edition (2011), 50 (18), 4127-4132, S4127/1-S4127/92CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
A strategy for the prepn. of glycoconjugated vaccines in which the site of attachment is well defined permitting site-specific protein conjugation is presented. Glycosyl disulfides are beneficial glycosyl donors for the synthesis of precursor oligosaccharides. Their aglycon flexibility allows a straightforward iterative assembly of complex carbohydrates contg. protective group freedom. Furthermore, the glycosyl disulfides advantageously deliver the thiol products suitable for site-specific protein ligation. Finally, since the use of pure, well-defined glycoproteins as potential immunogens is rare, this ability will allow insight into the effect of epitope positioning and immune response.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXkvFyrtLc%253D&md5=335c7b81ca4654ffc6d82ee8c1b1f574
52
Chalker, J. M.; Lercher, L.; Rose, N. R.; Schofield, C. J.; Davis, B. G. Angew. Chem., Int. Ed. 2012, 51, 1835
[ Crossref], [ PubMed], [ CAS], Google Scholar
52
Conversion of Cysteine into Dehydroalanine Enables Access to Synthetic Histones Bearing Diverse Post-Translational Modifications
Chalker, Justin M.; Lercher, Lukas; Rose, Nathan R.; Schofield, Christopher J.; Davis, Benjamin G.
Angewandte Chemie, International Edition (2012), 51 (8), 1835-1839, S1835/1-S1835/73CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
We have shown that Dha (dehydroalanine) is readily installed in histones by the reaction of the dibromide reagent 1 (a,a'-di-bromo-adipyl(bis)amide) with genetically incorporated Cys residues. Dha, in turn, is a chem. precursor to mimics of six distinct PTMs (post-translational modifications): mono-, di-, and trimethylated lysine, acetylated lysine, phosphorylated serine, and glycosylated serine. Through their combined use, we have shown ready switching of site and PTM type. The same modification could also be installed at multiple sites on a multi-milligram scale. To illustrate the potential of this technol., the first validation of phosphocysteine as a mimic of phosphoserine in any protein was described, the first access to a glycosylated histone was enabled, and the first direct observation of HDAC activity on an acetylated lysine mimic was reported for a full-length histone. The demonstrated interaction of our synthetic modified histones with both readers and writer/erasers shown here is a key step. Currently, we are exploring the use of the modified histones reported here as substrates for other chromatin-modifying enzymes.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xnt1ymsA%253D%253D&md5=db2acb39ab1d8da2380b137e70937a60
53
Fernández-González, M.; Boutureira, O.; Bernardes, G. J. L.; Chalker, J. M.; Young, M. A.; Errey, J. C.; Davis, B. G. Chem. Sci. 2010, 709
[ Crossref], [ CAS], Google Scholar
53
Site-selective chemoenzymatic construction of synthetic glycoproteins using endoglycosidases
Fernandez-Gonzalez, Marta; Boutureira, Omar; Bernardes, Goncalo J. L.; Chalker, Justin M.; Young, Matthew A.; Errey, James C.; Davis, Benjamin G.
Chemical Science (2010), 1 (6), 709-715CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)
Combined chem. tagging followed by Endo-A catalyzed elongation allows access to homogeneous, elaborated glycoproteins. A survey of different linkages and sugars demonstrated not only that unnatural linkages can be tolerated but they can provide insight into the scope of Endo-A transglycosylation activity. S-linked GlcNAc-glycoproteins are useful substrates for Endo-A extensions and display enhanced stability to hydrolysis at exposed sites. O-CH2-triazole-linked GlcNAc-glycoproteins derived from azidohomoalanine-tagged protein precursors were found to be optimal at sterically demanding sites.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhtl2nsLnE&md5=613c61342fa65cd1273e79866d7bead4
54
Aydillo, C.; Compañón, I.; Avenoza, A.; Busto, J. H.; Corzana, F.; Peregrina, J. M.; Zurbano, M. M. J. Am. Chem. Soc. 2014, 136, 789
[ ACS Full Text ], [ CAS], Google Scholar
54
S-Michael Additions to Chiral Dehydroalanines as an Entry to Glycosylated Cysteines and a Sulfa-Tn Antigen Mimic
Aydillo, Carlos; Companon, Ismael; Avenoza, Alberto; Busto, Jesus H.; Corzana, Francisco; Peregrina, Jesus M.; Zurbano, Maria M.
Journal of the American Chemical Society (2014), 136 (2), 789-800CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
Stereoselective sulfa-Michael addn. of appropriately protected thiocarbohydrates to chiral dehydroalanines has been developed as a key step in the synthesis of biol. important cysteine derivs., such as S-(β-D-glucopyranosyl)-D-cysteine, which has not been synthesized to date, and S-(2-acetamido-2-deoxy-α-D-galactopyranosyl)-L-cysteine, which could be considered as a mimic of Tn antigen. The corresponding diamide deriv. was also synthesized and analyzed from a conformational viewpoint, and its bound state with a lectin was studied.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXksVGm&md5=24177394496816c3440202ebe43941ce
55
Junutula, J. R.; Raab, H.; Clark, S.; Bhakta, S.; Leipold, D. D.; Weir, S.; Chen, Y.; Simpson, M.; Tsai, S. P.; Dennis, M. S.; Lu, Y.; Meng, Y. G.; Ng, C.; Yang, J.; Lee, C. C.; Duenas, E.; Gorrell, J.; Katta, V.; Kim, A.; McDorman, K.; Flagella, K.; Venook, R.; Ross, S.; Spencer, S. D.; Lee Wong, W.; Lowman, H. B.; Vandlen, R.; Sliwkowski, M. X.; Scheller, R. H.; Polakis, P.; Mallet, W. Nat. Biotechnol. 2008, 26, 925
[ Crossref], [ PubMed], [ CAS], Google Scholar
55
Site-specific conjugation of a cytotoxic drug to an antibody improves the therapeutic index
Junutula, Jagath R.; Raab, Helga; Clark, Suzanna; Bhakta, Sunil; Leipold, Douglas D.; Weir, Sylvia; Chen, Yvonne; Simpson, Michelle; Tsai, Siao Ping; Dennis, Mark S.; Lu, Yanmei; Meng, Y. Gloria; Ng, Carl; Yang, Jihong; Lee, Chien C.; Duenas, Eileen; Gorrell, Jeffrey; Katta, Viswanatham; Kim, Amy; McDorman, Kevin; Flagella, Kelly; Venook, Rayna; Ross, Sarajane; Spencer, Susan D.; Wong, Wai Lee; Lowman, Henry B.; Vandlen, Richard; Sliwkowski, Mark X.; Scheller, Richard H.; Polakis, Paul; Mallet, William
Nature Biotechnology (2008), 26 (8), 925-932CODEN: NABIF9; ISSN:1087-0156. (Nature Publishing Group)
Antibody-drug conjugates enhance the antitumor effects of antibodies and reduce adverse systemic effects of potent cytotoxic drugs. However, conventional drug conjugation strategies yield heterogeneous conjugates with relatively narrow therapeutic index (max. tolerated dose/curative dose). Using leads from the authors' previously described phage display-based method to predict suitable conjugation sites, the authors engineered cysteine substitutions at positions on light and heavy chains that provide reactive thiol groups and do not perturb Ig folding and assembly, or alter antigen binding. When conjugated to monomethyl auristatin E, an antibody against the ovarian cancer antigen MUC16 is as efficacious as a conventional conjugate in mouse xenograft models. Moreover, it is tolerated at higher doses in rats and cynomolgus monkeys than the same conjugate prepd. by conventional approaches. The favorable in vivo properties of the near-homogeneous compn. of this conjugate suggest that this strategy offers a general approach to retaining the antitumor efficacy of antibody-drug conjugates, while minimizing their systemic toxicity.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXps1Wmu7s%253D&md5=d55f59594fb6349d0337dfed2783e83c
56
(a) Steiner, M.; Hartmann, I.; Perrino, E.; Casi, G.; Brighton, S.; Jelesarov, I.; Bernardes, G. J. L.; Neri, D. Chem. Sci. 2013, 4, 297
[ Crossref], [ CAS], Google Scholar
56a
Spacer length shapes drug release and therapeutic efficacy of traceless disulfide-linked ADCs targeting the tumor neovasculature
Steiner, Martina; Hartmann, Isabelle; Perrino, Elena; Casi, Giulio; Brighton, Samatanga; Jelesarov, Ilian; Bernardes, Goncalo J. L.; Neri, Dario
Chemical Science (2013), 4 (1), 297-302CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)
We systematically investigated how the therapeutic efficacy of a traceless, vascular targeting antibody-drug conjugate (ADC) is affected by the length of a spacer introduced between the antibody's globular fold and the site of drug attachment. Homogeneous ADCs were prepd. from the direct conjugation of engineered C-terminal cysteines with a potent thiol contg. drug which was sepd. from the antibody surface by unstructured spacers of increasing length. We found that a smaller spacer length is reflected in enhanced stability and therapeutic efficacy of the conjugates in a syngeneic model of murine cancer.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhslKkurnM&md5=e4263b7e14041d12e46b0098868c40a0
(b) Bernardes, G. J. L.; Casi, G.; Trüssel, S.; Hartmann, I.; Schwager, K.; Scheuermann, J.; Neri, D. Angew. Chem., Int. Ed. 2012, 51, 941
[ Crossref], [ PubMed], [ CAS], Google Scholar
56b
A Traceless Vascular-Targeting Antibody-Drug Conjugate for Cancer Therapy
Bernardes, Goncalo J. L.; Casi, Giulio; Truessel, Sabrina; Hartmann, Isabelle; Schwager, Kathrin; Scheuermann, Joerg; Neri, Dario
Angewandte Chemie, International Edition (2012), 51 (4), 941-944, S941/1-S941/42CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
Monoclonal antibodies have demonstrated considerable utility in the clin. treatment of cancer, but unmodified Igs are rarely curative, esp. when used as single agents. Thus, there is considerable interest in arming antibodies with bioactive payloads (e.g., drugs, radionuclides, cytokines), to improve their potency and selectivity, thus increasing activity at the tumor site while sparing normal tissues. However, monoclonal antibodies specific to tumor cell antigens often exhibit limited diffusion into the solid tumor mass by several mechanisms, including slow extravasation and antibody trapping by perivascular tumor cells (the so-called antigen barrier). In view of the fact that the formation of new blood vessels (angiogenesis) is a rare process in a healthy adult but a characteristic feature of virtually all types of aggressive cancers, it would be reasonable to develop vascular-targeting antibody-dug conjugates (ADCs). In conclusion, a novel approach for the delivery of cytotoxic drugs using ADCs has been developed. Current ADCs target tumor cell surface markers and rely on the DC being internalized in the cells for drug delivery. Instead, our approach relies on targeting the tumor neo-vasculature offering comprehensive tumoral coverage.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhs1elurvI&md5=ca90b850dfb9fe9ce8ca598d694cf79b
(c) Perrino, E.; Steiner, M.; Krall, N.; Bernardes, G. J. L.; Pretto, F.; Casi, G.; Neri, D. Cancer Res. 2014, 74, 2569
[ Crossref], [ PubMed], [ CAS], Google Scholar
56c
Curative Properties of Noninternalizing Antibody-Drug Conjugates Based on Maytansinoids
Perrino, Elena; Steiner, Martina; Krall, Nikolaus; Bernardes, Goncalo J. L.; Pretto, Francesca; Casi, Giulio; Neri, Dario
Cancer Research (2014), 74 (9), 2569-2578CODEN: CNREA8; ISSN:0008-5472. (American Association for Cancer Research)
It is generally thought that the anticancer efficacy of antibody-drug conjugates (ADC) relies on their internalization by cancer cells. However, recent work on an ADC that targets fibronectin in the tumor microenvironment suggests this may not be necessary. The alternatively spliced extra domains A and B (EDA and EDB) of fibronectin offer appealing targets for ADC development, because the antigen is strongly expressed in many solid human tumors and nearly undetectable in normal tissues except for the female reproductive system. In this study, we describe the properties of a set of ADCs based on an antibody targeting the alternatively spliced EDA of fibronectin coupled to one of a set of potent cytotoxic drugs (DM1 or one of two duocarmycin derivs.). The DM1 conjugate SIP(F8)-SS-DM1 mediated potent antitumor activity in mice bearing DMl-sensitive F9 tumors but not DMl-insensitive CT26 tumors. Quant. biodistribution studies and microscopic analyses confirmed a preferential accumulation of SIP(F8)-SS-DM1 in the subendothelial extracellular matrix of tumors, similar to the pattern obsd. for unmodified antibody. Notably, we found that treatments were well tolerated at efficacious doses that were fully curative and compatible with pharmaceutical development. Our findings offer a preclin. proof-of-concept for curative ADC targeting the tumor microenvironment that do not rely upon antigen internalization.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXnt1arsro%253D&md5=183cf5ce0d4c3b74ebb0538f0233c0f6
(d) Bernardes, G. J. L.; Steiner, M.; Hartmann, I.; Neri, D.; Casi, G. Nat. Protoc. 2013, 8, 2079
[ Crossref], [ PubMed], [ CAS], Google Scholar
56d
Site-specific chemical modification of antibody fragments using traceless cleavable linkers
Bernardes, Goncalo J. L.; Steiner, Martina; Hartmann, Isabelle; Neri, Dario; Casi, Giulio
Nature Protocols (2013), 8 (11), 2079-2089CODEN: NPARDW; ISSN:1750-2799. (Nature Publishing Group)
Antibody-drug conjugates (ADCs) are promising agents for the selective delivery of cytotoxic drugs to specific cells (for example, tumors). In this protocol, we describe two strategies for the precise modification at engineered C- or N-terminal cysteines of antibodies in IgG, diabody and small immunoprotein (SIP) formats that yield homogenous ADCs. In this protocol, cemadotin derivs. are used as model drugs, as these agents have a potent cytotoxic activity and are easy to synthesize. However, other drugs with similar functional groups could be considered. In the first approach, a cemadotin deriv. contg. a sulfhydryl group results in a mixed disulfide linkage. In the second approach, a cemadotin deriv. contg. an aldehyde group is joined via a thiazolidine linkage. The procedures outlined are robust, enabling the prepn. of ADCs with a defined no. of drugs per antibody in a time frame between 7 and 24 h.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhsFGqtrfJ&md5=b878287531b0d108a73b802f3302dbfa
57
Casi, G.; Huguenin-Dezot, N.; Zuberbühler, K.; Scheuermann, J. r.; Neri, D. J. Am. Chem. Soc. 2012, 134, 5887
[ ACS Full Text ], [ CAS], Google Scholar
57
Site-Specific Traceless Coupling of Potent Cytotoxic Drugs to Recombinant Antibodies for Pharmacodelivery
Casi, Giulio; Huguenin-Dezot, Nicolas; Zuberbuhler, Kathrin; Scheuermann, Jorg; Neri, Dario
Journal of the American Chemical Society (2012), 134 (13), 5887-5892CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
Aldehyde drugs are gaining increasing research interest, considering that aldehyde dehydrogenases overexpression is characteristic of cancer stem cells. Here, we describe the traceless site-specific coupling of a novel potent drug, contg. an aldehyde moiety, to recombinant antibodies, which were engineered to display a cysteine residue at their N-terminus, or a 1,2-aminothiol at their C-terminus. The resulting chem. defined antibody-drug conjugates represent the first example in which a thiazolidine linkage is used for the targeted delivery and release of cytotoxic agents.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xjt1OgtLY%253D&md5=bb33caba8b47db0a47d3143d63655aa5
58
Yuan, Y.; Liang, G. Org. Biomol. Chem. 2014, 12, 865
[ Crossref], [ PubMed], [ CAS], Google Scholar
58
A biocompatible, highly efficient click reaction and its applications
Yuan, Yue; Liang, Gaolin
Organic & Biomolecular Chemistry (2014), 12 (6), 865-871CODEN: OBCRAK; ISSN:1477-0520. (Royal Society of Chemistry)
A review. Herein, we review the development, optimization, applications and potential prospects of a novel click reaction based on the condensation reaction between 2-cyanobenzothiazole (CBT) and D-cysteine (D-Cys) in fireflies. This click condensation reaction has obvious advantages in biocompatibility, efficiency and stability in aq. environments. Optimization of this click reaction has been carried out so that it can be controlled by pH change, redn., or enzymic cleavage to synthesize large mols. and self-assembled nanostructures, or enhance probe signals. Consequently, this CBT-based click reaction has been and could be successfully applied to a wide range of biomedical applications such as mol. imaging (e.g., optical imaging, nuclear imaging and magnetic resonance imaging), biomol. detection, drug delivery and other potentialities.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXnsFWgsQ%253D%253D&md5=9f35b5447ec48f6257b638902dc5875c
59
(a) Nathani, R. I.; Chudasama, V.; Ryan, C. P.; Moody, P. R.; Morgan, R. E.; Fitzmaurice, R. J.; Smith, M. E. B.; Baker, J. R.; Caddick, S. Org. Biomol. Chem. 2013, 11, 2408
[ Crossref], [ PubMed], [ CAS], Google Scholar
59a
Reversible protein affinity-labelling using bromomaleimide-based reagents
Nathani, Ramiz I.; Chudasama, Vijay; Ryan, Chris P.; Moody, Paul R.; Morgan, Rachel E.; Fitzmaurice, Richard J.; Smith, Mark E. B.; Baker, James R.; Caddick, Stephen
Organic & Biomolecular Chemistry (2013), 11 (15), 2408-2411CODEN: OBCRAK; ISSN:1477-0520. (Royal Society of Chemistry)
Reversible protein biotinylation is readily affected via conjugation with a bromomaleimide-based reagent followed by reductive cleavage. The intermediate biotinylated protein constructs are stable at physiol. temp. and pH 8.0. Quant. reversibility is elegantly delivered under mild conditions of using a stoichiometric amt. of a bis-thiol, thus providing an approach that will be of general interest in chem. biol. and proteomics.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXktlKisbY%253D&md5=a87a9d55027d35f95b095697601fb299
(b) Smith, M. E. B.; Schumacher, F. F.; Ryan, C. P.; Tedaldi, L. M.; Papaioannou, D.; Waksman, G.; Caddick, S.; Baker, J. R. J. Am. Chem. Soc. 2010, 132, 1960
[ ACS Full Text ], [ CAS], Google Scholar
59b
Protein Modification, Bioconjugation, and Disulfide Bridging Using Bromomaleimides
Smith, Mark E. B.; Schumacher, Felix F.; Ryan, Chris P.; Tedaldi, Lauren M.; Papaioannou, Danai; Waksman, Gabriel; Caddick, Stephen; Baker, James R.
Journal of the American Chemical Society (2010), 132 (6), 1960-1965CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
The maleimide motif is widely used for the selective chem. modification of cysteine residues in proteins. Despite widespread utilization, there are some potential limitations, including the irreversible nature of the reaction and, hence, the modification and the no. of attachment positions. The authors conceived of a new class of maleimide which would address some of these limitations and provide new opportunities for protein modification. The authors report herein the use of mono- and dibromomaleimides for reversible cysteine modification and illustrate this on the SH2 domain of the Grb2 adaptor protein (L111C). After initial modification of a protein with a bromo- or dibromomaleimide, it is possible to add an equiv. of a second thiol to give further bioconjugation, demonstrating that bromomaleimides offer opportunities for up to three points of attachment. The resultant protein-maleimide products can be cleaved to regenerate the unmodified protein by addn. of a phosphine or a large excess of a thiol. Furthermore, dibromomaleimide can insert into a disulfide bond, forming a maleimide bridge, and this is illustrated on the peptide hormone somatostatin. Fluorescein-labeled dibromomaleimide is synthesized and inserted into the disulfide to construct a fluorescent somatostatin analog. These results highlight the significant potential for this new class of reagents in protein modification.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXptl2rug%253D%253D&md5=0ed793a9db6ef7384d8b64294d0cecc8
60
Moody, P.; Smith, M. E. B.; Ryan, C. P.; Chudasama, V.; Baker, J. R.; Molloy, J.; Caddick, S. ChemBioChem 2012, 13, 39
[ Crossref], [ PubMed], [ CAS], Google Scholar
60
Bromomaleimide-Linked Bioconjugates Are Cleavable in Mammalian Cells
Moody, Paul; Smith, Mark. E. B.; Ryan, Chris P.; Chudasama, Vijay; Baker, James R.; Molloy, Justin; Caddick, Stephen
ChemBioChem (2012), 13 (1), 39-41CODEN: CBCHFX; ISSN:1439-4227. (Wiley-VCH Verlag GmbH & Co. KGaA)
The synthesis of bromomaleimide-linked bioconjugates was carried out to demonstrate that bromomaleimide-linked bioconjugates were cleaved in the cytoplasm of mammalian cells.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhsVOktL7N&md5=be902af98c65c468943336de07dfdf94
61
Marculescu, C.; Kossen, H.; Morgan, R. E.; Mayer, P.; Fletcher, S. A.; Tolner, B.; Chester, K. A.; Jones, L. H.; Baker, J. R. Chem. Commun. 2014, 50, 7139
[ Crossref], [ PubMed], [ CAS], Google Scholar
61
Aryloxymaleimides for cysteine modification, disulfide bridging and the dual functionalization of disulfide bonds
Marculescu, Cristina; Kossen, Hanno; Morgan, Rachel E.; Mayer, Patrick; Fletcher, Sally A.; Tolner, Berend; Chester, Kerry A.; Jones, Lyn H.; Baker, James R.
Chemical Communications (Cambridge, United Kingdom) (2014), 50 (54), 7139-7142CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
Tuning the properties of maleimide reagents holds significant promise in expanding the toolbox of available methods for bioconjugation. Herein the authors describe aryloxymaleimides which represent next generation maleimides of attenuated reactivity and demonstrate their ability to enable new methods for protein modification at disulfide bonds.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtVagt7fK&md5=b1149186edd6b0e678b4beb8e7d4f72a
62
(a) Lyon, R. P.; Setter, J. R.; Bovee, T. D.; Doronina, S. O.; Hunter, J. H.; Anderson, M. E.; Balasubramanian, C. L.; Duniho, S. M.; Leiske, C. I.; Li, F.; Senter, P. D. Nat. Biotechnol. 2014, 32, 1059
[ Crossref], [ PubMed], [ CAS], Google Scholar
62a
Self-hydrolyzing maleimides improve the stability and pharmacological properties of antibody-drug conjugates
Lyon, Robert P.; Setter, Jocelyn R.; Bovee, Tim D.; Doronina, Svetlana O.; Hunter, Joshua H.; Anderson, Martha E.; Balasubramanian, Cindy L.; Duniho, Steven M.; Leiske, Chris I.; Li, Fu; Senter, Peter D.
Nature Biotechnology (2014), 32 (10), 1059-1062CODEN: NABIF9; ISSN:1087-0156. (Nature Publishing Group)
Many antibody-drug conjugates (ADCs) are unstable in vivo because they are formed from maleimide-contg. components conjugated to reactive thiols. These thiosuccinimide linkages undergo two competing reactions in plasma: elimination of the maleimide through a retro-Michael reaction, which results in loss of drug-linker from the ADC, and hydrolysis of the thiosuccinimide ring, which results in a deriv. that is resistant to the elimination reaction. In an effort to create linker technologies with improved stability characteristics, we used diaminopropionic acid (DPR) to prep. a drug-linker incorporating a basic amino group adjacent to the maleimide, positioned to provide intramol. catalysis of thiosuccinimide ring hydrolysis. This basic group induces the thiosuccinimide to undergo rapid hydrolysis at neutral pH and room temp. Once hydrolyzed, the drug-linker is no longer subject to maleimide elimination reactions, preventing nonspecific deconjugation. In vivo studies demonstrate that the increased stability characteristics can lead to improved ADC antitumor activity and reduced neutropenia.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsFKms7jN&md5=96c3b19b856cc9c685cbdc704a842797
(b) Tumey, L. N.; Charati, M.; He, T.; Sousa, E.; Ma, D.; Han, X.; Clark, T.; Casavant, J.; Loganzo, F.; Barletta, F.; Lucas, J.; Graziani, E. I. Bioconjugate Chem. 2014, 25, 1871
[ ACS Full Text ], [ CAS], Google Scholar
62b
Mild Method for Succinimide Hydrolysis on ADCs: Impact on ADC Potency, Stability, Exposure, and Efficacy
Tumey, L. Nathan; Charati, Manoj; He, Tao; Sousa, Eric; Ma, Dangshe; Han, Xiaogang; Clark, Tracey; Casavant, Jeff; Loganzo, Frank; Barletta, Frank; Lucas, Judy; Graziani, Edmund I.
Bioconjugate Chemistry (2014), 25 (10), 1871-1880CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
The stability of the connection between the antibody and the toxin can have a profound impact on ADC safety and efficacy. There has been increasing evidence in recent years that maleimide-based ADCs are prone to payload loss via a retro-Michael type reaction. Herein, we report a mild method for the hydrolysis of the succinimide-thioether ring which results in a "ring-opened" linker. ADCs contg. this hydrolyzed succinimide linker show equiv. cytotoxicity, improved in vitro stability, improved PK exposure, and improved efficacy as compared to their nonhydrolyzed counterparts. This method offers a simple way to improve the stability, exposure, and efficacy of maleimide-based ADCs.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsFelsb3F&md5=a680174dc91b2ce9a3c72b6519a6c231
(c) Fontaine, S. D.; Reid, R.; Robinson, L.; Ashley, G. W.; Santi, D. V. Bioconjugate Chem. 2015, 26, 145
[ ACS Full Text ], [ CAS], Google Scholar
62c
Long-Term Stabilization of Maleimide-Thiol Conjugates
Fontaine, Shaun D.; Reid, Ralph; Robinson, Louise; Ashley, Gary W.; Santi, Daniel V.
Bioconjugate Chemistry (2015), 26 (1), 145-152CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
The rates of ring-opening hydrolysis and retro-Michael/Michael addn. (thiol exchange) of N-substituted succinimide thioethers formed by maleimide-thiol conjugation with glutathione and the effects of their maleimide nitrogen substituents on the rates of maleimide hydrolysis and retro-Michael/Michael addn. reactions were detd. Ring-opening of conjugates prepd. with commonly used maleimides were too slow to serve as prevention against thiol exchange; however, the ring-opening rates of maleimides were greatly accelerated by electron withdrawing N-substituents, and the products had half-lives of over two years. The PEGylated antibody Cimzia underwent ring-opening and retro-Michael addns. with rates consistent with model compds. except for the difference in acidity of the internal cysteine thiol of Cimizia's antibody vs. the nearly terminal cysteine thiols of the model compds. Thus, conjugates (particularly antibody-drug conjugates prepd. as drugs) made with maleimides possessing electron-deficient nitrogen substituents can be purposefully hydrolyzed to their ring-opened counterparts in vitro to ensure their in vivo stability to thiol cleavage and exchange reactions.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXitFCrsrfN&md5=ab4fcacf5f9f58159bafa50353eab4d5
63
Chudasama, V.; Smith, M. E. B.; Schumacher, F. F.; Papaioannou, D.; Waksman, G.; Baker, J. R.; Caddick, S. Chem. Commun. 2011, 47, 8781
[ Crossref], [ PubMed], [ CAS], Google Scholar
63
Bromopyridazinedione-mediated protein and peptide bioconjugation
Chudasama, Vijay; Smith, Mark E. B.; Schumacher, Felix F.; Papaioannou, Danai; Waksman, Gabriel; Baker, James R.; Caddick, Stephen
Chemical Communications (Cambridge, United Kingdom) (2011), 47 (31), 8781-8783CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
Bromopyridazinedione-mediated bioconjugation to a cysteine contg. protein and a disulfide contg. peptide is described. The conjugates are cleavable in an excess of thiol, including cytoplasmically-relevant concns. of glutathione, and show a high level of hydrolytic stability. The constructs have the potential for four points of chem. attachment.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXpt1Kru7Y%253D&md5=0d8615a135eb11522e0809328902aab4
64
Maruani, A.; Alom, S.; Canavelli, P.; Lee, M. T. W.; Morgan, R. E.; Chudasama, V.; Caddick, S. Chem. Commun. 2015, DOI: 10.1039/C4CC08515A
[ Crossref], Google Scholar
There is no corresponding record for this reference.
65
Nathani, R.; Moody, P.; Smith, M. E. B.; Fitzmaurice, R. J.; Caddick, S. ChemBioChem 2012, 13, 1283
[ Crossref], [ PubMed], [ CAS], Google Scholar
65
Bioconjugation of Green Fluorescent Protein via an Unexpectedly Stable Cyclic Sulfonium Intermediate
Nathani, Ramiz; Moody, Paul; Smith, Mark E. B.; Fitzmaurice, Richard J.; Caddick, Stephen
ChemBioChem (2012), 13 (9), 1283-1285CODEN: CBCHFX; ISSN:1439-4227. (Wiley-VCH Verlag GmbH & Co. KGaA)
Treatment of a cysteine mutant (S147C) of superfolder green fluorescent protein (GFP) with bis-alkylating agents can be used to prep. highly stable, yet synthetically useful cyclic protein sulfonium adducts. These species undergo clean addn. reactions to allow the introduction of a variety of useful chem. motifs. It was envisaged that the stability of the generated cysteine-derived sulfonium is presumably strongly correlated to the chem. environment of the alkylated cysteine. This new bioconjugation technique could provide a useful entry into multiply functionalized proteins and further work will be directed toward extending these findings to other systems.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XnsFyjur4%253D&md5=e075d1a428cc74bbd50854a882711091
66
Nathani, R. I.; Moody, P.; Chudasama, V.; Smith, M. E. B.; Fitzmaurice, R. J.; Caddick, S. Chem. Sci. 2013, 4, 3455
[ Crossref], [ PubMed], [ CAS], Google Scholar
66
A novel approach to the site-selective dual labelling of a protein via chemoselective cysteine modification
Nathani, Ramiz I.; Moody, Paul; Chudasama, Vijay; Smith, Mark E. B.; Fitzmaurice, Richard J.; Caddick, Stephen
Chemical Science (2013), 4 (9), 3455-3458CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)
Local protein microenvironment is used to control the outcome of reaction between cysteine residues and 2,5-dibromohexanediamide. The differential reactivity is exploited to introduce two orthogonal reactive handles onto the surface of a double cysteine mutant of superfolder green fluorescent protein in a regioselective manner. Subsequent elaboration with commonly used thiol and alkyne contg. reagents affects site-selective protein dual labeling.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtFOks7jF&md5=5162cef2d39eba5c8944bda9f142cf31
67
Shiu, H.-Y.; Chan, T.-C.; Ho, C.-M.; Liu, Y.; Wong, M.-K.; Che, C.-M. Chem.—Eur. J. 2009, 15, 3839
[ Crossref], [ PubMed], [ CAS], Google Scholar
67
Electron-deficient alkynes as cleavable reagents for the modification of cysteine-containing peptides in aqueous medium
Shiu, Hoi-Yan; Chan, Tak-Chung; Ho, Chi-Ming; Liu, Yungen; Wong, Man-Kin; Che, Chi-Ming
Chemistry - A European Journal (2009), 15 (15), 3839-3850CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)
An efficient method has been developed for the chemoselective cysteine modification of unprotected peptides and proteins in aq. media through the formation of a vinyl sulfide linkage by using electron-deficient alkynes, including alkynoic amides, esters and alky-nones. The terminal alky-none-modified peptides could be converted back into the unmodified peptides (81% isolated yield) by adding thiols under mild conditions. The usefulness of this thiol-assisted cleavage of the vinyl sulfide linkage in peptides has been exemplified by the enrichment of a cysteine-contg. peptide (71% recovery) from a mixt. of cysteine-contg. and non-cysteine-contg. peptides.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXksleitr0%253D&md5=cdf4acf18e4737c673a807ed1968aae6
68
Shiu, H.-Y.; Chong, H.-C.; Leung, Y.-C.; Zou, T.; Che, C.-M. Chem. Commun. 2014, 50, 4375
[ Crossref], [ PubMed], [ CAS], Google Scholar
68
Phosphorescent proteins for bio-imaging and site selective bio-conjugation of peptides and proteins with luminescent cyclometalated iridium(iii) complexes
Shiu, Hoi-Yan; Chong, Hiu-Chi; Leung, Yun-Chung; Zou, Taotao; Che, Chi-Ming
Chemical Communications (Cambridge, United Kingdom) (2014), 50 (33), 4375-4378CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
A new bio-conjugation reaction for site selective modification of proteins and peptides with phosphorescent iridium(iii) complexes has been developed; the Ir(iii)-modified proteins and peptides display long emission lifetimes and large Stoke shifts that can be used for bio-imaging studies.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXltFajs7c%253D&md5=ac5e56bacfe9a9c7a40245a97bed6529
69
Koniev, O.; Leriche, G.; Nothisen, M.; Remy, J.-S.; Strub, J.-M.; Schaeffer-Reiss, C.; Van Dorsselaer, A.; Baati, R.; Wagner, A. Bioconjugate Chem. 2014, 25, 202
[ ACS Full Text ], [ CAS], Google Scholar
69
Selective Irreversible Chemical Tagging of Cysteine with 3-Arylpropiolonitriles
Koniev, Oleksandr; Leriche, Geoffray; Nothisen, Marc; Remy, Jean-Serge; Strub, Jean-Marc; Schaeffer-Reiss, Christine; Van Dorsselaer, Alain; Baati, Rachid; Wagner, Alain
Bioconjugate Chemistry (2014), 25 (2), 202-206CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
Exquisite chemoselectivity for cysteine has been found for a novel class of remarkably hydrolytically stable reagents, 3-arylpropiolonitriles (APN). The efficacy of the APN-mediated tagging was benchmarked against other cysteine-selective methodologies in a model study on a series of traceable amino acid derivs. The selectivity of the methodol. was further explored on peptide mixts. obtained by trypsin digestion of lysozyme. Addnl., the superior stability of APN-cysteine conjugates in aq. media, human plasma, and living cells makes this new thiol-click reaction a promising methodol. for applications in bioconjugation.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXmtl2nsQ%253D%253D&md5=6a55f6f7c3ca774016d6c92c5e21812c
70
Arumugam, S.; Guo, J.; Mbua, N. E.; Friscourt, F.; Lin, N.; Nekongo, E.; Boons, G.-J.; Popik, V. V. Chem. Sci. 2014, 5, 1591
[ Crossref], [ PubMed], [ CAS], Google Scholar
70
Selective and reversible photochemical derivatization of cysteine residues in peptides and proteins
Arumugam, Selvanathan; Guo, Jun; Mbua, Ngalle Eric; Friscourt, Frederic; Lin, Nannan; Nekongo, Emmanuel; Boons, Geert-Jan; Popik, Vladimir V.
Chemical Science (2014), 5 (4), 1591-1598CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)
The selective derivatization of solvent-exposed cysteine residues in peptides and proteins is achieved by brief irradn. of an aq. soln. contg. 3-(hydroxymethyl)-2-naphthol derivs. (NQMPs) with a 350 nm fluorescent lamp. NQMP can be conjugated with various moieties, such as PEG, dyes, carbohydrates, or possess a fragment for further selective derivatization, e.g., biotin, azide, alkyne, etc. Attractive features of this labeling approach include an exceptionally fast rate of the reaction and a requirement for a low equivalence of the reagent. The NQMP-thioether linkage is stable under ambient conditions, and survives protein digestion and MS anal. Irradn. of an NQMP-labeled protein in a dil. soln. (<40 μM) or in the presence of a vinyl ether results in a traceless release of the substrate. The reversible biotinylation of bovine serum albumin (BSA), as well as the capture and release of this protein using NeutrAvidin Agarose resin beads has been demonstrated.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXjsVekurs%253D&md5=dc009e216182fe84df3741223c380d7d
71
Zhang, D.; Devarie-Baez, N. O.; Li, Q.; Lancaster, J. R.; Xian, M. Org. Lett. 2012, 14, 3396
[ ACS Full Text ], [ CAS], Google Scholar
71
Methylsulfonyl Benzothiazole (MSBT): A Selective Protein Thiol Blocking Reagent
Zhang, Dehui; Devarie-Baez, Nelmi O.; Li, Qian; Lancaster, Jack R.; Xian, Ming
Organic Letters (2012), 14 (13), 3396-3399CODEN: ORLEF7; ISSN:1523-7052. (American Chemical Society)
A new thiol blocking reagent, methylsulfonyl benzothiazole, was discovered. This reagent showed good selectivity and high reactivity for protein thiols.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xot1antL8%253D&md5=6e785b51e6288197559db5a91a982a9a
72
Toda, N.; Asano, S.; Barbas, C. F. Angew. Chem., Int. Ed. 2013, 52, 12592
[ Crossref], [ PubMed], [ CAS], Google Scholar
72
Rapid, stable, chemoselective labeling of thiols with Julia-Kocienski-like reagents: A serum-stable alternative to maleimide-based protein conjugation
Toda, Narihiro; Asano, Shigehiro; Barbas, Carlos F., III
Angewandte Chemie, International Edition (2013), 52 (48), 12592-12596CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
We have developed a class of sulfone derivs. for applications in protein conjugation chem., and we have compared the newly synthesized conjugates to maleimide conjugates. Methylsulfonyl-functionalized five-membered cyclic compds., such as phenyltetrazole or phenyloxadiazole, reacted rapidly and specifically with thiols in small mols. and proteins with exquisite chemoselectivity at biol. relevant pH values (pH 5.8 - 8.0). Designer heteroarom. sulfones allowed for the selective introduction of a fluorophore and poly(ethylene) glycol chains (PEGylation), and provided protein conjugates with superior stability compared to maleimide-conjugated proteins in human plasma. Given the speed, selectivity, and stability of the sulfone-cysteine reactions described herein, we anticipate that this "thiol-Click" approach will find broad application in peptide and protein chem. and for the development of antibody drug conjugates.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhs1Wms7%252FF&md5=ef91e1e933d116482b9e886c94c6cdd0
73
Patterson, J. T.; Asano, S.; Li, X.; Rader, C.; Barbas, C. F. Bioconjugate Chem. 2014, 25, 1402
[ ACS Full Text ], [ CAS], Google Scholar
73
Improving the Serum Stability of Site-Specific Antibody Conjugates with Sulfone Linkers
Patterson, James T.; Asano, Shigehiro; Li, Xiuling; Rader, Christoph; Barbas, Carlos F., III
Bioconjugate Chemistry (2014), 25 (8), 1402-1407CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
Current routes for synthesizing antibody-drug conjugates commonly rely on maleimide linkers to react with cysteine thiols. However, thioether exchange with metabolites and serum proteins can compromise conjugate stability and diminish in vivo efficacy. We report the application of a phenyloxadiazole sulfone linker for the prepn. of trastuzumab conjugates. This sulfone linker site-specifically labeled engineered cysteine residues in THIOMABs and improved antibody conjugate stability in human plasma at sites previously shown to be labile for maleimide conjugates. Similarly, sulfone conjugation with selenocysteine in an anti-ROR1 scFv-Fc improved human plasma stability relative to maleimide conjugation. Kinetically controlled labeling of a THIOMAB contg. two cysteine substitutions was also achieved, offering a strategy for producing antibody conjugates with expanded valency.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXht12gu77I&md5=1692372289fc0c7dabf1374851b5ccd6
74
Abbas, A.; Xing, B.; Loh, T.-P. Angew. Chem., Int. Ed. 2014, 53, 7491
[ Crossref], [ PubMed], [ CAS], Google Scholar
74
Allenamides as Orthogonal Handles for Selective Modification of Cysteine in Peptides and Proteins
Abbas, Ata; Xing, Bengang; Loh, Teck-Peng
Angewandte Chemie, International Edition (2014), 53 (29), 7491-7494CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
In this study, a remarkably simple and direct strategy has been successfully developed to selectively label target cysteine residues in fully unprotected peptides and proteins. The strategy is based on the reaction between allenamides and the cysteine thiol, and proceeds swiftly in aq. medium with excellent selectivity and quant. conversion, thus forming a stable and irreversible conjugate. The combined simplicity and mildness of the process project allenamide as robust and versatile handles to target cysteines and has potential use in biol. systems. Addnl., fluorescent-labeling studies demonstrated that the installation of a C-terminal allenamide moiety onto various mols. of interest may supply a new methodol. towards the site-specific labeling of cysteine-contg. proteins. Such a new labeling strategy may thus open a window for its application in the field of life sciences.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXovVKltb0%253D&md5=bd00e8d70e768cf9a4b84422b2ee10ed
75
Lutolf, M. P.; Tirelli, N.; Cerritelli, S.; Cavalli, L.; Hubbell, J. A. Bioconjugate Chem. 2001, 12, 1051
[ ACS Full Text ], [ CAS], Google Scholar
75
Systematic Modulation of Michael-Type Reactivity of Thiols through the Use of Charged Amino Acids
Lutolf, M. P.; Tirelli, N.; Cerritelli, S.; Colussi, L.; Hubbell, J. A.
Bioconjugate Chemistry (2001), 12 (6), 1051-1056CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
A quant. structure-reactivity relationship for the Michael-type addn. of thiols onto acrylates was detd. Several thiol-contg. peptides were investigated by examg. the correlation between the second-order rate const. of their addn. onto PEG-diacrylate and the pKa of the thiols within a peptide. By introducing charged amino acids in close proximity to a cysteine, the pKa of the thiol was systematically modulated by electrostatic interactions. Pos. charges from the amino acid arginine decreased the pKa of the thiol and accelerated the reaction with acrylates while neg. charges from aspartic acids showed the opposite effect. A linear correlation between thiolate concns. and kinetic consts. was found, confirming the role of thiolates as the reactive species in this Michael-type reaction. The relevant factors influencing the reactivity were the sign and the no. of the neighboring charges, while the position of these charges had little effect on reactivity. These results provide a basis for the rational design of peptides, where the kinetics, and thus, selectivity of protein/peptide conjugation with polymeric structures via Michael-type addn. reactions can be controlled.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3MXmvFSgtr0%253D&md5=cb14139b26a0fdf4070841d9b2e383d5
76
Ma, F.-H.; Chen, J.-L.; Li, Q.-F.; Zuo, H.-H.; Huang, F.; Su, X.-C. Chem.—Asian J. 2014, 9, 1808
[ Crossref], [ PubMed], [ CAS], Google Scholar
76
Kinetic Assay of the Michael Addition-Like Thiol-Ene Reaction and Insight into Protein Bioconjugation
Ma, Fei-He; Chen, Jia-Liang; Li, Qing-Feng; Zuo, Hui-Hui; Huang, Feng; Su, Xun-Cheng
Chemistry - An Asian Journal (2014), 9 (7), 1808-1816CODEN: CAAJBI; ISSN:1861-4728. (Wiley-VCH Verlag GmbH & Co. KGaA)
The chem. modification of proteins is a valuable technique in understanding the functions, interactions, and dynamics of proteins. Reactivity and selectivity are key issues in current chem. modification of proteins. The Michael addn.-like thiol-ene reaction is a useful tool that can be used to tag proteins with high selectivity for the solvent-exposed thiol groups of proteins. To obtain insight into the bioconjugation of proteins with this method, a kinetic anal. was performed. New vinyl-substituted pyridine derivs. were designed and synthesized. The reactivity of these vinyl tags with L-cysteine was evaluated by UV absorption and high-resoln. NMR spectroscopy. The results show that protonation of pyridine plays a key role in the overall reaction rates. The kinetic parameters were assessed in protein modification. The different reactivities of these vinyl tags with solvent-exposed cysteine is valuable information in the selective labeling of proteins with multiple functional groups.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXosV2gsro%253D&md5=e4878dfc5437061ec2b42f5098341589
77
Moody, P.; Chudasama, V.; Nathani, R. I.; Maruani, A.; Martin, S.; Smith, M. E. B.; Caddick, S. Chem. Commun. 2014, 50, 4898
[ Crossref], [ PubMed], [ CAS], Google Scholar
77
A rapid, site-selective and efficient route to the dual modification of DARPins
Moody, Paul; Chudasama, Vijay; Nathani, Ramiz I.; Maruani, Antoine; Martin, Stephen; Smith, Mark E. B.; Caddick, Stephen
Chemical Communications (Cambridge, United Kingdom) (2014), 50 (38), 4898-4900CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
Designed ankyrin repeat proteins (DARPins) are valuable tools in both biochem. and medicine. Herein we describe a rapid, simple method for the dual modification of DARPins by introduction of cysteine mutations at specific positions that results in a vast difference in their thiol nucleophilicity, allowing for clean sequential modification.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXmtlertrg%253D&md5=d084af56b20d37e36f6e13b3eadace30
78
Shen, B.-Q.; Xu, K.; Liu, L.; Raab, H.; Bhakta, S.; Kenrick, M.; Parsons-Reponte, K. L.; Tien, J.; Yu, S.-F.; Mai, E.; Li, D.; Tibbitts, J.; Baudys, J.; Saad, O. M.; Scales, S. J.; McDonald, P. J.; Hass, P. E.; Eigenbrot, C.; Nguyen, T.; Solis, W. A.; Fuji, R. N.; Flagella, K. M.; Patel, D.; Spencer, S. D.; Khawli, L. A.; Ebens, A.; Wong, W. L.; Vandlen, R.; Kaur, S.; Sliwkowski, M. X.; Scheller, R. H.; Polakis, P.; Junutula, J. R. Nat. Biotechnol. 2012, 30, 184
[ Crossref], [ PubMed], [ CAS], Google Scholar
78
Conjugation site modulates the in vivo stability and therapeutic activity of antibody-drug conjugates
Shen, Ben-Quan; Xu, Keyang; Liu, Luna; Raab, Helga; Bhakta, Sunil; Kenrick, Margaret; Parsons-Reponte, Kathryn L.; Tien, Janet; Yu, Shang-Fan; Mai, Elaine; Li, Dongwei; Tibbitts, Jay; Baudys, Jakub; Saad, Ola M.; Scales, Suzie J.; McDonald, Paul J.; Hass, Philip E.; Eigenbrot, Charles; Nguyen, Trung; Solis, Willy A.; Fuji, Reina N.; Flagella, Kelly M.; Patel, Darshana; Spencer, Susan D.; Khawli, Leslie A.; Ebens, Allen; Wong, Wai Lee; Vandlen, Richard; Kaur, Surinder; Sliwkowski, Mark X.; Scheller, Richard H.; Polakis, Paul; Junutula, Jagath R.
Nature Biotechnology (2012), 30 (2), 184-189CODEN: NABIF9; ISSN:1087-0156. (Nature Publishing Group)
The reactive thiol in cysteine is used for coupling maleimide linkers in the generation of antibody conjugates. To assess the impact of the conjugation site, we engineered cysteines into a therapeutic HER2/neu antibody at three sites differing in solvent accessibility and local charge. The highly solvent-accessible site rapidly lost conjugated thiol-reactive linkers in plasma owing to maleimide exchange with reactive thiols in albumin, free cysteine or glutathione. In contrast, a partially accessible site with a pos. charged environment promoted hydrolysis of the succinimide ring in the linker, thereby preventing this exchange reaction. The site with partial solvent-accessibility and neutral charge displayed both properties. In a mouse mammary tumor model, the stability and therapeutic activity of the antibody conjugate were affected pos. by succinimide ring hydrolysis and neg. by maleimide exchange with thiol-reactive constituents in plasma. Thus, the chem. and structural dynamics of the conjugation site can influence antibody conjugate performance by modulating the stability of the antibody-linker interface.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtVGqtLg%253D&md5=c647fc5bdfe93dfdabb15ca40934837f
79
(a) Valkevich, E. M.; Guenette, R. G.; Sanchez, N. A.; Chen, Y.-C.; Ge, Y.; Strieter, E. R. J. Am. Chem. Soc. 2012, 134, 6916
[ ACS Full Text ], [ CAS], Google Scholar
79a
Forging Isopeptide Bonds Using Thiol-Ene Chemistry: Site-Specific Coupling of Ubiquitin Molecules for Studying the Activity of Isopeptidases
Valkevich, Ellen M.; Guenette, Robert G.; Sanchez, Nicholas A.; Chen, Yi-chen; Ge, Ying; Strieter, Eric R.
Journal of the American Chemical Society (2012), 134 (16), 6916-6919CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
Chem. methods for modifying proteins can enable studies aimed at uncovering biochem. function. Herein, we describe the use of thiol-ene coupling (TEC) chem. to report on the function of branched (also referred to as forked) ubiquitin trimers. We show how site-specific isopeptide (Nε-Gly-l-homothiaLys) bonds are forged between two mols. of Ub, demonstrating the power of TEC in protein conjugation. Moreover, we demonstrate that the Nε-Gly-l-homothiaLys isopeptide bond is processed to a similar extent by deubiquitinases (DUBs) as that of a native Nε-Gly-l-Lys isopeptide bond, thereby establishing the utility of TEC in the generation of Ub-Ub linkages. TEC is then applied to the synthesis of branched Ub trimers. Interrogation of these branched derivs. with DUBs reveals that the relative orientation of the two Ub units has a dramatic impact on how they are hydrolyzed. In particular, cleavage of K48C-linkages is suppressed when the central Ub unit is also conjugated through K6C, whereas cleavage proceeds normally when the central unit is conjugated through either K11C or K63C. The results of this work presage a role for branched polymeric Ub chains in regulating linkage-selective interactions.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xltl2hsb0%253D&md5=48a15faed42b65562a907de08f67bbdb
(b) Li, F.; Allahverdi, A.; Yang, R.; Lua, G. B. J.; Zhang, X.; Cao, Y.; Korolev, N.; Nordenskiöld, L.; Liu, C.-F. Angew. Chem., Int. Ed. 2011, 50, 9611
[ Crossref], [ PubMed], [ CAS], Google Scholar
79b
A Direct Method for Site-Specific Protein Acetylation
Li, Fupeng; Allahverdi, Abdollah; Yang, Renliang; Lua, Gavian Bing Jia; Zhang, Xiaohong; Cao, Yuan; Korolev, Nikolay; Nordenskioeld, Lars; Liu, Chuan-Fa
Angewandte Chemie, International Edition (2011), 50 (41), 9611-9614, S9611/1-S9611/18CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
A previously unexplored thiol-ene radical addn. reaction involving the com. available N-vinyl acetamide (NVA) is well suited for the S-acetamidoethylation of cysteine residues in synthetic peptides and recombinant proteins. The resultant N-acetyl-thialysine differs from natural acetyllysine only isosterically at the γ position of the amino acid structure and is functionally equiv. or similar to the latter. Although a limitation of the method is that the protein substrates should not contain other cysteines, it nevertheless has many potential applications, such as the histone epigenetic study--an intense research area at present. The reaction system is robust and gives near quant. yields of site-specifically acetylated proteins that can be purified in a simple chromatog. or dialysis step. The ease of implementation of this method also makes it easily adoptable for researchers from the bioscience research community. As such, this radical reaction approach provides a convenient enabling tool for the study of lysine acetylation biol. and will help to advance research in this important field.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhtFyls77K&md5=1a6488f091750257ec6519746d0010b3
80
Conte, M. L.; Staderini, S.; Marra, A.; Sánchez-Navarro, M.; Davis, B. G.; Dondoni, A. Chem. Commun. 2011, 47, 11086
[ Crossref], [ PubMed], Google Scholar
There is no corresponding record for this reference.
81
(a) Chen, S.; Touati, J.; Heinis, C. Chem. Commun. 2014, 50, 5267
[ Crossref], [ PubMed], [ CAS], Google Scholar
81a
Tracking chemical reactions on the surface of filamentous phage using mass spectrometry
Chen, Shiyu; Touati, Jeremy; Heinis, Christian
Chemical Communications (Cambridge, United Kingdom) (2014), 50 (40), 5267-5269CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
Chem. modification of phage libraries has allowed the in vitro evolution of ligands having properties not provided by natural polypeptides. The development of novel and more diverse chem. reactions on phage was hampered by the lack of anal. methods to efficiently monitor the reaction products on the more than 10 000 kDa large filamentous phage particles. Herein, we present a strategy to detect chem. modified peptides on phage based on enzymic release of peptide from phage and mass spectrometry anal.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXmsFequrs%253D&md5=84bce15829da90551b84a6a8aec46dd5
(b) Chen, S.; Bertoldo, D.; Angelini, A.; Pojer, F.; Heinis, C. Angew. Chem., Int. Ed. 2014, 53, 1602
[ Crossref], [ PubMed], [ CAS], Google Scholar
81b
Peptide Ligands Stabilized by Small Molecules
Chen, Shiyu; Bertoldo, Davide; Angelini, Alessandro; Pojer, Florence; Heinis, Christian
Angewandte Chemie, International Edition (2014), 53 (6), 1602-1606CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
Bicyclic peptides generated through directed evolution by using phage display offer an attractive ligand format for the development of therapeutics. Being nearly 100-fold smaller than antibodies, they promise advantages such as access to chem. synthesis, efficient diffusion into tissues, and needle-free application. However, unlike antibodies, they do not have a folded structure in soln. and thus do not bind as well as antibodies. We developed bicyclic peptides with hydrophilic chem. structures at their center to promote noncovalent intramol. interactions, thereby stabilizing the peptide conformation. The sequences of the peptides isolated by phage display from large combinatorial libraries were strongly influenced by the type of small mol. used in the screen, thus suggesting that the peptides fold around the small mols. X-ray structure anal. revealed that the small mols. indeed formed hydrogen bonds with the peptides. These noncovalent interactions stabilize the peptide-protein complexes and contribute to the high binding affinity.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtVyltLc%253D&md5=4bc852345c54171bd8c7143a563bba2b
(c) Angelini, A.; Diderich, P.; Morales-Sanfrutos, J.; Thurnheer, S.; Hacker, D.; Menin, L.; Heinis, C. Bioconjugate Chem. 2012, 23, 1856
[ ACS Full Text ], [ CAS], Google Scholar
81c
Chemical Macrocyclization of Peptides Fused to Antibody Fc Fragments
Angelini, Alessandro; Diderich, Philippe; Morales-Sanfrutos, Julia; Thurnheer, Sarah; Hacker, David; Menin, Laure; Heinis, Christian
Bioconjugate Chemistry (2012), 23 (9), 1856-1863CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
To extend the plasma half-life of a bicyclic peptide antagonist, we chose to link it to the Fc fragment of the long-lived serum protein IgG1. Instead of chem. conjugating the entire bicyclic peptide, we recombinantly expressed its peptide moiety as a fusion protein to an Fc fragment and subsequently cyclized the peptide by chem. reacting its three cysteine residues with tris-(bromomethyl)benzene. This reaction was efficient and selective, yielding completely modified peptide fusion protein and no side products. After optimization of the linker and the Fc fragment format, the bicyclic peptide was fully functional as an inhibitor (Ki = 76 nM) and showed an extended terminal half-life of 1.5 days in mice. The unexpectedly clean reaction makes chem. macrocyclization of peptide-Fc fusion proteins an attractive synthetic approach. Its good compatibility with the Fc fragment may lend the bromomethylbenzene-based chem. also for the generation of antibody-drug conjugates.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtVGntrrJ&md5=8b935079985721863d5833e472013824
(d) Angelini, A.; Heinis, C. Curr. Opin. Chem. Biol. 2011, 15, 355
[ Crossref], [ PubMed], [ CAS], Google Scholar
81d
Post-translational modification of genetically encoded polypeptide libraries
Angelini, Alessandro; Heinis, Christian
Current Opinion in Chemical Biology (2011), 15 (3), 355-361CODEN: COCBF4; ISSN:1367-5931. (Elsevier B.V.)
The genetic encoding of polypeptides with biol. display systems enables the facile generation and screening of very large combinatorial libraries of mols. By post-translationally modifying the encoded polypeptides, chem. and structurally more diverse mols. beyond linear amino acid polymers can be generated. The first post-translational modification applied to encoded polypeptides, the oxidn. of cysteine residues to form disulfide bridges, is a natural one and was used to cyclise short peptides soon after the invention of phage display. Recently a range of non-natural chem. strategies for the post-translational modification of encoded polypeptide repertoires were applied to generate optical biosensors, semisynthetic polypeptides, peptide-drug conjugates, redox-insensitive monocyclic peptides or multicyclic peptides, and these strategies are reviewed in this article.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXntV2lur0%253D&md5=e866df303755fc97722fc56344e8b1d7
(e) Heinis, C.; Rutherford, T.; Freund, S.; Winter, G. Nat. Chem. Biol. 2009, 5, 502
[ Crossref], [ PubMed], [ CAS], Google Scholar
81e
Phage-encoded combinatorial chemical libraries based on bicyclic peptides
Heinis, Christian; Rutherford, Trevor; Freund, Stephan; Winter, Greg
Nature Chemical Biology (2009), 5 (7), 502-507CODEN: NCBABT; ISSN:1552-4450. (Nature Publishing Group)
Here we describe a phage strategy for the selection of ligands based on bicyclic or linear peptides attached covalently to an org. core. We designed peptide repertoires with three reactive cysteine residues, each spaced apart by several random amino acid residues, and we fused the repertoires to the phage gene-3-protein. Conjugation with tris-(bromomethyl)benzene via the reactive cysteines generated repertoires of peptide conjugates with two peptide loops anchored to a mesitylene core. Iterative affinity selections yielded several enzyme inhibitors; after further mutagenesis and selection, we were able to chem. synthesize a lead inhibitor (PK15; Ki = 1.5 nM) specific to human plasma kallikrein that efficiently interrupted the intrinsic coagulation pathway in human plasma tested ex vivo. This approach offers a powerful means of generating and selecting bicyclic macrocycles (or if cleaved, linear derivs. thereof) as ligands poised at the interface of small-mol. drugs and biologics.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXms1altbs%253D&md5=0634460f77b185fbcf85309c6dbf93e3
82
Fukunaga, K.; Hatanaka, T.; Ito, Y.; Minami, M.; Taki, M. Chem. Commun. 2014, 50, 3921
[ Crossref], [ PubMed], [ CAS], Google Scholar
82
Construction of a crown ether-like supramolecular library by conjugation of genetically-encoded peptide linkers displayed on bacteriophage T7
Fukunaga, Keisuke; Hatanaka, Takaaki; Ito, Yuji; Minami, Michiko; Taki, Masumi
Chemical Communications (Cambridge, United Kingdom) (2014), 50 (30), 3921-3923CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
By using the 10BASEd-T, the authors synthesized a crown ether-like macrocyclic library possessing randomized peptide linkers on bacteriophage T7. Among 1.5 × 109 diversities of the supramol. candidates, the authors have obtained a specific binder for the N-terminal domain of Hsp90.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXks1Srtbc%253D&md5=5ddeebf7fc041122e3fbbcb7ca233189
83
Bellotto, S.; Chen, S.; Rentero Rebollo, I.; Wegner, H. A.; Heinis, C. J. Am. Chem. Soc. 2014, 136, 5880
[ ACS Full Text ], [ CAS], Google Scholar
83
Phage Selection of Photoswitchable Peptide Ligands
Bellotto, Silvia; Chen, Shiyu; Rentero Rebollo, Inmaculada; Wegner, Hermann A.; Heinis, Christian
Journal of the American Chemical Society (2014), 136 (16), 5880-5883CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
Photoswitchable ligands are powerful tools to control biol. processes at high spatial and temporal resoln. Unfortunately, such ligands exist only for a limited no. of proteins and their development by rational design is not trivial. We have developed an in vitro evolution strategy to generate light-activatable peptide ligands to targets of choice. In brief, random peptides were encoded by phage display, chem. cyclized with an azobenzene linker, exposed to UV light to switch the azobenzene into cis conformation, and panned against the model target streptavidin. Isolated peptides shared strong consensus sequences, indicating target-specific binding. Several peptides bound with high affinity when cyclized with the azobenzene linker, and their affinity could be modulated by UV light. The presented method is robust and can be applied for the in vitro evolution of photoswitchable ligands to virtually any target.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXls1Crsb4%253D&md5=28162c9cf4f3e0b367caea44b515276e
84
(a) Zou, Y.; Spokoyny, A. M.; Zhang, C.; Simon, M. D.; Yu, H.; Lin, Y.-S.; Pentelute, B. L. Org. Biomol. Chem. 2014, 12, 566
[ Crossref], [ PubMed], [ CAS], Google Scholar
84a
Convergent diversity-oriented side-chain macrocyclization scan for unprotected polypeptides
Zou, Yekui; Spokoyny, Alexander M.; Zhang, Chi; Simon, Mark D.; Yu, Hongtao; Lin, Yu-Shan; Pentelute, Bradley L.
Organic & Biomolecular Chemistry (2014), 12 (4), 566-573CODEN: OBCRAK; ISSN:1477-0520. (Royal Society of Chemistry)
Here we describe a general synthetic platform for side-chain macrocyclization of an unprotected peptide library based on the SNAr reaction between cysteine thiolates and a new generation of highly reactive perfluoro-arom. small mol. linkers. This strategy enabled us to simultaneously "scan" two cysteine residues positioned from i, i + 1 to i, i + 14 sites in a polypeptide, producing 98 macrocyclic products from reactions of 14 peptides with 7 linkers. A complementary reverse strategy was developed; cysteine residues within the polypeptide were first modified with non-bridging perfluoroaryl moieties and then com. available dithiol linkers were used for macrocyclization. The highly convergent, site-independent, and modular nature of these two strategies coupled with the unique chemoselectivity of a SNAr transformation allows for the rapid diversity-oriented synthesis of hybrid macrocyclic peptide libraries with varied chem. and structural complexities.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhvFKhsbvF&md5=ae75e82db7691c038b604e5fd2a80f4a
(b) Zhang, C.; Dai, P.; Spokoyny, A. M.; Pentelute, B. L. Org. Lett. 2014, 16, 3652
[ ACS Full Text ], [ CAS], Google Scholar
84b
Enzyme-Catalyzed Macrocyclization of Long Unprotected Peptides
Zhang, Chi; Dai, Peng; Spokoyny, Alexander M.; Pentelute, Bradley L.
Organic Letters (2014), 16 (14), 3652-3655CODEN: ORLEF7; ISSN:1523-7052. (American Chemical Society)
A glutathione S-transferase (GST) catalyzed macrocyclization reaction for peptides up to 40 amino acids in length is reported. GST catalyzes the selective SNAr reaction between an N-terminal glutathione (GSH, γ-Glu-Cys-Gly) tag and a C-terminal perfluoroaryl-modified cysteine on the same polypeptide chain. Cyclic peptides ranging from 9 to 24 residues were quant. produced within 2 h in aq. pH = 8 buffer at room temp. The reaction was highly selective for cyclization at the GSH tag, enabling the combination of GST-catalyzed ligation with native chem. ligation to generate a large 40-residue peptide macrocycle.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtFWjtLzJ&md5=ed8a6b70496b596a8fd509b30ffe3db9
(c) Zhang, C.; Spokoyny, A. M.; Zou, Y.; Simon, M. D.; Pentelute, B. L. Angew. Chem., Int. Ed. 2013, 52, 14001
[ Crossref], [ PubMed], [ CAS], Google Scholar
84c
Enzymatic "Click" Ligation: Selective Cysteine Modification in Polypeptides Enabled by Promiscuous Glutathione S-Transferase
Zhang, Chi; Spokoyny, Alexander M.; Zou, Yekui; Simon, Mark D.; Pentelute, Bradley L.
Angewandte Chemie, International Edition (2013), 52 (52), 14001-14005CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
Naturally occurring glutathione S-transferase (GST) was used to catalyze an efficient "click" ligation between polypeptides with an N-terminal glutathione sequence and biomols. or chem. probes contg. perfluorinated arom. groups. The site-specific modification of one cysteine residue was possible in the presence of other unprotected cysteine residues and reactive functional groups.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhslOlt77F&md5=447585b915fad3dfcdc56d58c5c2a8c7
85
Griffin, B. A.; Adams, S. R.; Tsien, R. Y. Science 1998, 281, 269
[ Crossref], [ PubMed], [ CAS], Google Scholar
85
Specific covalent labeling of recombinant protein molecules inside live cells
Griffin, B. Albert; Adams, Stephen R.; Tsein, Roger Y.
Science (Washington, D. C.) (1998), 281 (5374), 269-272CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)
Recombinant proteins contg. four cysteines at the i, i + 1, i + 4, and i + 5 positions of a α helix were fluorescently labeled in living cells by extracellular administration of 4',5'-bis(1,3,2-dithioarsolan-2-yl)fluorescein. This designed small ligand is membrane-permeant and nonfluorescent until it binds with high affinity and specificity to the tetracysteine domain. Such in situ labeling adds much less mass than does green fluorescent protein and offers greater versatility in attachment sites as well as potential spectroscopic and chem. properties. This system provides a recipe for slightly modifying a target protein so that it can be singled out from the many other proteins inside live cells and fluorescently stained by small nonfluorescent dye mols. added from outside the cells.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK1cXksFKgs78%253D&md5=3d9867443016af9eb20745ed39b578a1
86
Kim, T. H.; Swierczewska, M.; Oh, Y.; Kim, A.; Jo, D. G.; Park, J. H.; Byun, Y.; Sadegh-Nasseri, S.; Pomper, M. G.; Lee, K. C.; Lee, S. Angew. Chem., Int. Ed. 2013, 52, 6880
[ Crossref], [ CAS], Google Scholar
86
Mix to Validate: A Facile, Reversible PEGylation for Fast Screening of Potential Therapeutic Proteins In Vivo
Kim, Tae Hyung; Swierczewska, Magdalena; Oh, Yumin; Kim, Ae Ryon; Jo, Dong Gyu; Park, Jae Hyung; Byun, Youngro; Sadegh-Nasseri, Scheherazade; Pomper, Martin G.; Lee, Kang Choon; Lee, Seulki
Angewandte Chemie, International Edition (2013), 52 (27), 6880-6884CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
The authors introduce a facile technique that allows for efficacy testing of protein drugs in animal models by extending the half-life in the blood of any selected protein candidate without compromising bioactivity. This technique offers the benefits of site-specific PEGylation without time-consuming and costly chem. modification and purifn. processes, enabling high-throughput testing of protein drugs in vivo. The general concept used is to PEGylate proteins through a complementary interaction between an oligo-histidine tag (His-tag) and a Ni2+ complex of nitrilotriacetic acid (NTA), which is now widely used in protein research. For example, protein immobilization techniques and protein labeling with fluorophores use the properties of a His-tag binding to NTA. The tumor necrosis factor-related apoptosis inducing ligand (TRAIL) was chosen as a model protein drug. The general design of reactive Ni-NTA-PEG analogs, and its binding to a His-tag, hexahistidine (H6), and fused protein are illustrated. Using TRAIL as a model protein, we demonstrated that a unique Ni-NTA-PEG analog assocd. with a His-tagged protein is able to provide outstanding physicochem. stability without compromising the bioactivity. Importantly, the Ni-NTA-PEG analog maximized the pharmacol. efficacy of the protein drug in vivo.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXptVantbo%253D&md5=9be70b55fc73724485eb58f41dfd3a92
87
(a) Rashidian, M.; Dozier, J. K.; Distefano, M. D. Bioconjugate Chem. 2013, 24, 1277
[ ACS Full Text ], [ CAS], Google Scholar
87a
Enzymatic Labeling of Proteins: Techniques and Approaches
Rashidian, Mohammad; Dozier, Jonathan K.; Distefano, Mark D.
Bioconjugate Chemistry (2013), 24 (8), 1277-1294CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
A review. Site-specific modification of proteins is a major challenge in modern chem. biol. due to the large no. of reactive functional groups typically present in polypeptides. Because of its importance in biol. and medicine, the development of methods for site-specific modification of proteins is an area of intense research. Selective protein modification procedures have been useful for oriented protein immobilization, for studies of naturally occurring post-translational modifications, for creating antibody-drug conjugates, for the introduction of fluorophores and other small mols. on to proteins, for examg. protein structure, folding, dynamics, and protein-protein interactions, and for the prepn. of protein-polymer conjugates. One of the most important approaches for protein labeling is to incorporate bioorthogonal functionalities into proteins at specific sites via enzymic reactions. The incorporated tags then enable reactions that are chemoselective, whose functional groups not only are inert in biol. media, but also do not occur natively in proteins or other macromols. This review article summarizes the enzymic strategies, which enable site-specific functionalization of proteins with a variety of different functional groups. The enzymes covered in this review include formylglycine generating enzyme, sialyltransferases, phosphopantetheinyltransferases, O-GlcNAc post-translational modification, sortagging, transglutaminase, farnesyltransferase, biotin ligase, lipoic acid ligase, and N-myristoyltransferase.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtVKku77P&md5=4197395b3554983f91f4eade70197dbe
(b) Rashidian, M.; Kumarapperuma, S. C.; Gabrielse, K.; Fegan, A.; Wagner, C. R.; Distefano, M. D. J. Am. Chem. Soc. 2013, 135, 16388
[ ACS Full Text ], [ CAS], Google Scholar
87b
Simultaneous Dual Protein Labeling Using a Triorthogonal Reagent
Rashidian, Mohammad; Kumarapperuma, Sidath C.; Gabrielse, Kari; Fegan, Adrian; Wagner, Carston R.; Distefano, Mark D.
Journal of the American Chemical Society (2013), 135 (44), 16388-16396CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
Construction of heterofunctional proteins is a rapidly emerging area of biotherapeutics. Combining a protein with other moieties, such as a targeting element, a toxic protein or small mol., and a fluorophore or polyethylene glycol (PEG) group, can improve the specificity, functionality, potency, and pharmacokinetic profile of a protein. Protein farnesyl transferase (PFTase) is able to site-specifically and quant. prenylate proteins contg. a C-terminal CaaX-box amino acid sequence with various modified isoprenoids. Here, the authors describe the design, synthesis, and application of a triorthogonal reagent (I) that can be used to site-specifically incorporate an alkyne and aldehyde group simultaneously into a protein. To illustrate the capabilities of this approach, a protein was enzymically modified with compd. I followed by oxime ligation and click reaction to simultaneously incorporate an azido-tetramethylrhodamine (TAMRA) fluorophore and an aminooxy-PEG moiety. This was performed with both a model protein [green fluorescent protein (GFP)] as well as a therapeutically useful protein [ciliary neurotrophic factor (CNTF)]. Next, a protein was enzymically modified with compd. I followed by coupling to an azido-bis-methotrexate dimerizer and aminooxy-TAMRA. Incubation of that construct with a dihydrofolate reductase (DHFR)-DHFR-anti-CD3 fusion protein resulted in the self-assembly of nanoring structures that were endocytosed into T-leukemia cells and visualized therein. These results highlight how complex multifunctional protein assemblies can be prepd. using this facile triorthogonal approach.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhs1CktLbK&md5=882648fafd4196fe3c6c590862d7e496
88
Uchinomiya, S.; Ojida, A.; Hamachi, I. Inorg. Chem. 2014, 53, 1816
[ ACS Full Text ], [ CAS], Google Scholar
88
Peptide Tag/Probe Pairs Based on the Coordination Chemistry for Protein Labeling
Uchinomiya, Shohei; Ojida, Akio; Hamachi, Itaru
Inorganic Chemistry (2014), 53 (4), 1816-1823CODEN: INOCAJ; ISSN:0020-1669. (American Chemical Society)
A review. Protein-labeling methods serve as essential tools for analyzing functions of proteins of interest under complicated biol. conditions such as in live cells. These labeling methods are useful not only to fluorescently visualize proteins of interest in biol. systems but also to conduct protein and cell analyses by harnessing the unique functions of mol. probes. Among the various labeling methods available, an appropriate binding pair consisting of a short peptide and a de novo designed small mol. probe has attracted attention because of its wide utility and versatility. Most peptide tag/probe pairs exploit metal-ligand coordination interactions as the main binding force responsible for their assocn. Herein, the authors provide an overview of the recent progress of these coordination-chem.-based protein-labeling methods and their applications for fluorescence imaging and functional anal. of cellular proteins, while highlighting the authors' originally developed labeling methods. These successful examples clearly exemplify the utility and versatility of metal coordination chem. in protein functional anal.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhs1Wlt7nF&md5=6ba4ee9432b0acb842b3f7629f0b6474
89
(a) Chen, X.-H.; Xiang, Z.; Hu, Y. S.; Lacey, V. K.; Cang, H.; Wang, L. ACS Chem. Biol. 2014, 9, 1956
[ ACS Full Text ], [ CAS], Google Scholar
89a
Genetically Encoding an Electrophilic Amino Acid for Protein Stapling and Covalent Binding to Native Receptors
Chen, Xiao-Hua; Xiang, Zheng; Hu, Ying S.; Lacey, Vanessa K.; Cang, Hu; Wang, Lei
ACS Chemical Biology (2014), 9 (9), 1956-1961CODEN: ACBCCT; ISSN:1554-8929. (American Chemical Society)
Covalent bonds can be generated within and between proteins by an unnatural amino acid (Uaa) reacting with a natural residue through proximity-enabled bioreactivity. Until now, Uaas have been developed to react mainly with cysteine in proteins. Here the authors genetically encoded an electrophilic Uaa capable of reacting with histidine and lysine, thereby expanding the diversity of target proteins and the scope of the proximity-enabled protein crosslinking technol. In addn. to efficient crosslinking of proteins inter- and intramolecularly, this Uaa permits direct stapling of a protein α-helix in a recombinant manner and covalent binding of native membrane receptors in live cells. The target diversity, recombinant stapling, and covalent targeting of endogenous proteins enabled by this versatile Uaa should prove valuable in developing novel research tools, biol. diagnostics, and therapeutics by exploiting covalent protein linkages for specificity, irreversibility, and stability.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtFeisbrE&md5=4938b2a7b1f9e72d050811a5e5ed0bc0
(b) Furman, J. L.; Kang, M.; Choi, S.; Cao, Y.; Wold, E. D.; Sun, S. B.; Smider, V. V.; Schultz, P. G.; Kim, C. H. J. Am. Chem. Soc. 2014, 136, 8411
[ ACS Full Text ], [ CAS], Google Scholar
89b
A Genetically Encoded aza-Michael Acceptor for Covalent Cross-Linking of Protein-Receptor Complexes
Furman, Jennifer L.; Kang, Mingchao; Choi, Seihyun; Cao, Yu; Wold, Erik D.; Sun, Sophie B.; Smider, Vaughn V.; Schultz, Peter G.; Kim, Chan Hyuk
Journal of the American Chemical Society (2014), 136 (23), 8411-8417CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
Selective covalent bond formation at a protein-protein interface potentially can be achieved by genetically introducing into a protein an appropriately "tuned" electrophilic unnatural amino acid that reacts with a native nucleophilic residue in its cognate receptor upon complex formation. We have evolved orthogonal aminoacyl-tRNA synthetase/tRNACUA pairs that genetically encode three aza-Michael acceptor amino acids, Nε-acryloyl-(S)-lysine (AcrK, 1), p-acrylamido-(S)-phenylalanine (AcrF, 2), and p-vinylsulfonamido-(S)-phenylalanine (VSF, 3), in response to the amber stop codon in Escherichia coli. Using an αErbB2 Fab-ErbB2 antibody-receptor pair as an example, we demonstrate covalent bond formation between an αErbB2-VSF mutant and a sp. surface lysine ε-amino group of ErbB2, leading to near quant. crosslinking to either purified ErbB2 in vitro or to native cellular ErbB2 at physiol. pH. This efficient biocompatible reaction may be useful for creating novel cell biol. probes, diagnostics, or therapeutics that selectively and irreversibly bind a target protein in vitro or in living cells.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXosVSqtbc%253D&md5=bfd340b02d54ec4367b4785f2a49633c
(c) Lu, Y.; Huang, F.; Wang, J.; Xia, J. Bioconjugate Chem. 2014, 25, 989
[ ACS Full Text ], [ CAS], Google Scholar
89c
Affinity-Guided Covalent Conjugation Reactions Based on PDZ-Peptide and SH3-Peptide Interactions
Lu, Yao; Huang, Feng; Wang, Jianpeng; Xia, Jiang
Bioconjugate Chemistry (2014), 25 (5), 989-999CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
Specific protein-peptide interactions are prevalent in the living cells and form a tightly regulated signaling network. These interactions, many of which have structural information revealed, provide ideal templates for affinity-guided covalent bioconjugation. Here we report the development of a set of four new reactions that covalently and site-specifically link nonenzymic scaffolding domains (two PDZ and two SH3 domains) and their ligands through thiol-chloroacetyl SN2 reaction. Guided by the three-dimensional structure of the wild type complex, a selected position of the protein was mutated to cysteine, and at the same time, an α-chloroacetyl group was installed at a corresponding position of the peptide. Specific binding interaction between the two brings the reactive groups into close proximity, converts the nonreactive cysteine residue into a content-dependent reactive site, and induces the nucleophilic reaction that is inert in the absence of the binding event. The specificity, orthogonality, and modularity of the four reactions were characterized, the reaction was applied to label proteins in vitro and receptor on the surface of mammalian cells, and the system was utilized to assemble covalent protein complexes with unnatural geometries.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXmt1Gjt7o%253D&md5=56257c8fa44ec69c3df3587178bad393
(d) Xiang, Z.; Lacey, V. K.; Ren, H.; Xu, J.; Burban, D. J.; Jennings, P. A.; Wang, L. Angew. Chem., Int. Ed. 2014, 53, 2190
[ Crossref], [ PubMed], [ CAS], Google Scholar
89d
Proximity-Enabled Protein Crosslinking through Genetically Encoding Haloalkane Unnatural Amino Acids
Xiang, Zheng; Lacey, Vanessa K.; Ren, Haiyan; Xu, Jing; Burban, David J.; Jennings, Patricia A.; Wang, Lei
Angewandte Chemie, International Edition (2014), 53 (8), 2190-2193CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
The selective generation of covalent bonds between and within proteins would provide new avenues for studying protein function and engineering proteins with new properties. New covalent bonds were genetically introduced into proteins by enabling an unnatural amino acid (Uaa) to selectively react with a proximal natural residue. This proximity-enabled bioreactivity was expanded to a series of haloalkane Uaas. Orthogonal tRNA/synthetase pairs were evolved to incorporate these Uaas, which only form a covalent thioether bond with cysteine when positioned in close proximity. By using the Uaa and cysteine, spontaneous covalent bond formation was demonstrated between an affibody and its substrate Z protein, thereby leading to irreversible binding, and within the affibody to increase its thermostability. This strategy of proximity-enabled protein crosslinking (PEPC) may be generally expanded to target different natural amino acids, thus providing diversity and flexibility in covalent bond formation for protein research and protein engineering.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtVygurk%253D&md5=e6e50075baae0dcf7fbdab1b64287bf3
(e) Masuya, T.; Murai, M.; Ifuku, K.; Morisaka, H.; Miyoshi, H. Biochemistry 2014, 53, 2307
[ ACS Full Text ], [ CAS], Google Scholar
89e
Site-Specific Chemical Labeling of Mitochondrial Respiratory Complex I through Ligand-Directed Tosylate Chemistry
Masuya, Takahiro; Murai, Masatoshi; Ifuku, Kentaro; Morisaka, Hironobu; Miyoshi, Hideto
Biochemistry (2014), 53 (14), 2307-2317CODEN: BICHAW; ISSN:0006-2960. (American Chemical Society)
The site-specific chem. modification of NADH-quinone oxidoreductase (complex I) by various functional probes such as fluorophores and microbeads, without affecting the enzyme activity, may allow single-mol. analyses of putative dynamic conformational changes in the enzyme. In an attempt to address this challenge, we performed site-specific alkynylation of complex I in bovine heart submitochondrial particles by means of a ligand-directed tosylate (LDT) chem. strategy with synthetic acetogenin ligand 1, which has an alkynylated tosylate in the tail moiety, as a high-affinity ligand against the enzyme. The terminal alkyne was chosen as the tag to be incorporated into the enzyme because this functional group can serve as a "footing" for subsequent diverse chem. modifications via so-called click chem. (i.e., azide-alkyne [3+2] cycloaddn. in water). To identify the position alkynylated by ligand 1, fluorescent tetramethylrhodamine was covalently attached to the incorporated alkyne by click chem. after the solubilization of complex I. Detailed proteomic analyses revealed that alkynylation occurred at Asp160 in the 49 kDa subunit, which may be located in the inner part of the putative quinone-binding cavity. The alkynylation was completely suppressed in the presence of an excess of other inhibitors such as bullatacin and quinazoline. While the reaction yield of the alkynylation step via LDT chem. was estd. to be ∼50%, the alkynylation unfortunately resulted in the almost complete inhibition of enzyme activity. Nevertheless, the results of this study demonstrate that complex I can be site-specifically alkynylated through LDT chem., providing a clue about the diverse chem. modifications of the enzyme in combination with click chem.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXks1yrsb8%253D&md5=c9c119588420607931bc99947e802247
(f) Hayashi, T.; Sun, Y.; Tamura, T.; Kuwata, K.; Song, Z.; Takaoka, Y.; Hamachi, I. J. Am. Chem. Soc. 2013, 135, 12252
[ ACS Full Text ], [ CAS], Google Scholar
89f
Semisynthetic Lectin-4-Dimethylaminopyridine Conjugates for Labeling and Profiling Glycoproteins on Live Cell Surfaces
Hayashi, Takahiro; Sun, Yedi; Tamura, Tomonori; Kuwata, Keiko; Song, Zhining; Takaoka, Yousuke; Hamachi, Itaru
Journal of the American Chemical Society (2013), 135 (33), 12252-12258CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
Glycoproteins on cell surfaces play important roles in biol. processes, including cell-cell interaction/signaling, immune response, and cell differentiation. Given the diversity of the structure of glycans, labeling and imaging of selected glycoproteins are challenging, although several promising strategies have been developed recently. Here, we design and construct semisynthetic reactive lectins (sugar-binding proteins) that are able to selectively label glycoproteins. Congerin II, an animal galectin, and wheat germ agglutinin are conjugated with 4-dimethylaminopyridine (DMAP), a well-known acyl transfer catalyst by our affinity-guided DMAP method and Cu(I)-assisted click chem. Selective labeling of glycoproteins is facilitated by the DMAP-tethered lectin catalysts both in vitro and on living cells. Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) anal. enabled us to isolate labeled glycoproteins that are uniquely exposed on distinct cell lines. Furthermore, the combination of immunopptn. with mass spectrometry (MS)-fingerprinting techniques allowed us to characterize 48 glycoproteins endogenously expressed on HeLa cells, and some low-abundant glycoproteins, such as epidermal growth factor receptor (EGFR) and neuropilin-1, were successfully identified. Our results demonstrate that semisynthetic DMAP-tethered lectins provide a new tool for labeling and profiling glycoproteins on living cells.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtFOltrjN&md5=87a7d74c4cfa15e0918b2aaa2b4bf2f3
(g) Uchinomiya, S.; Nonaka, H.; Wakayama, S.; Ojida, A.; Hamachi, I. Chem. Commun. 2013, 49, 5022
[ Crossref], [ PubMed], [ CAS], Google Scholar
89g
In-cell covalent labeling of reactive His-tag fused proteins
Uchinomiya, Shohei; Nonaka, Hiroshi; Wakayama, Sho; Ojida, Akio; Hamachi, Itaru
Chemical Communications (Cambridge, United Kingdom) (2013), 49 (44), 5022-5024CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
A new method for in-cell protein labeling was developed. This method employed a binding-induced nucleophilic reaction between the Cys-appended His-tag and the Ni(II)-NTA contg. an α-chloroacetamide. Using this method, not only labeling of His-tag fused proteins but also the detection of a protein-protein interaction was achieved inside living cells.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXntlaisrc%253D&md5=c1e81acd59aa9ecff7d3b41ed7abb5ec
(h) Tamura, T.; Tsukiji, S.; Hamachi, I. J. Am. Chem. Soc. 2012, 134, 2216
[ ACS Full Text ], [ CAS], Google Scholar
89h
Native FKBP12 Engineering by Ligand-Directed Tosyl Chemistry: Labeling Properties and Application to Photo-Cross-Linking of Protein Complexes in Vitro and in Living Cells
Tamura, Tomonori; Tsukiji, Shinya; Hamachi, Itaru
Journal of the American Chemical Society (2012), 134 (4), 2216-2226CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
The ability to modify target native (endogenous) proteins selectively in living cells with synthetic mols. should provide powerful tools for chem. biol. To this end, the authors recently developed a novel protein labeling technique termed ligand-directed tosyl (LDT) chem. This method uses labeling reagents in which a protein ligand and a synthetic probe are connected by a tosylate ester group. The authors previously demonstrated its applicability to the selective chem. labeling of several native proteins in living cells and mice. However, many fundamental features of this chem. remain to be studied. In this work, the authors investigated the relation between the LDT reagent structure and labeling properties by using native FK506-binding protein 12 (FKBP12) as a target protein. In vitro expts. revealed that the length and rigidity of the spacer structure linking the protein ligand and the tosylate group have significant effects on the overall labeling yield and labeling site. In addn. to histidine, which the authors reported previously, tyrosine and glutamate residues were identified as amino acids that are modified by LDT-mediated labeling. Through the screening of various spacer structures, piperazine was optimal for FKBP12 labeling in terms of labeling efficiency and site specificity. Using a piperazine-based LDT reagent contg. a photoreactive probe, the authors successfully demonstrated the labeling and UV-induced covalent crosslinking of FKBP12 and its interacting proteins in vitro and in living cells. This study not only furthers the understanding of the basic reaction properties of LDT chem. but also extends the applicability of this method to the investigation of biol. processes in mammalian cells.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XivVWrsg%253D%253D&md5=928d74d5f63d2be4a9b2b40baf7b5982
(i) Fujishima, S.-h.; Yasui, R.; Miki, T.; Ojida, A.; Hamachi, I. J. Am. Chem. Soc. 2012, 134, 3961
[ ACS Full Text ], [ CAS], Google Scholar
89i
Ligand-Directed Acyl Imidazole Chemistry for Labeling of Membrane-Bound Proteins on Live Cells
Fujishima, Sho-hei; Yasui, Ryosuke; Miki, Takayuki; Ojida, Akio; Hamachi, Itaru
Journal of the American Chemical Society (2012), 134 (9), 3961-3964CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
Chem.-based protein labeling in living cells is undoubtedly useful for understanding natural protein functions and for biol./pharmaceutical applications. Here, the authors report a novel approach for endogenous membrane-bound protein labeling for both in vitro and live cell conditions. A moderately reactive alkyloxyacyl imidazole (AI) assisted by ligand-binding affinity (ligand-directed AI (LDAI)) chem. allowed the authors to selectively modify natural proteins, such as dihydrofolate reductase (DHFR) and folate receptor (FR), neither of which could be efficiently labeled using the recently developed ligand-directed tosylate approach. It was clear that LDAI selectively labeled a single Lys(K32) in DHFR, proximal to the ligand-binding pocket. The authors also demonstrate that the fluorescein-labeled (endogenous, by LDAI) FR works as a fluorescent biosensor on the live KB cell surface, which allowed the authors to carry out unprecedented in situ kinetic anal. of ligand binding to FR.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XislSqu7w%253D&md5=6ccb65da77cad1b62892b738f42e1c55
(j) Wang, H.; Koshi, Y.; Minato, D.; Nonaka, H.; Kiyonaka, S.; Mori, Y.; Tsukiji, S.; Hamachi, I. J. Am. Chem. Soc. 2011, 133, 12220
[ ACS Full Text ], [ CAS], Google Scholar
89j
Chemical Cell-Surface Receptor Engineering Using Affinity-Guided, Multivalent Organocatalysts
Wang, Hangxiang; Koshi, Yoichiro; Minato, Daishiro; Nonaka, Hiroshi; Kiyonaka, Shigeki; Mori, Yasuo; Tsukiji, Shinya; Hamachi, Itaru
Journal of the American Chemical Society (2011), 133 (31), 12220-12228CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
Catalysts hold promise as tools for chem. protein modification. However, the application of catalysts or catalyst-mediated reactions to proteins has only recently begun to be addressed, mainly in in vitro systems. By radically improving the affinity-guided DMAP (4-dimethylaminopyridine) (AGD) catalysts that the authors previously reported, here the authors have developed a new organocatalyst-based approach that allows specific chem. acylation of a receptor protein on the surface of live cells. The catalysts consist of a set of multivalent DMAP groups (the acyl transfer catalyst) fused to a ligand specific to the target protein. It was clearly demonstrated by in vitro expts. that the catalyst multivalency enables remarkable enhancement of protein acylation efficiency in the labeling of three different proteins: congerin II, a Src homol. 2 (SH2) domain, and FKBP12. Using a multivalent AGD catalyst and optimized acyl donors contg. a chosen probe, the authors successfully achieved selective chem. labeling of bradykinin B2 receptor (B2R), a G-protein coupled receptor, on the live cell-surface. Furthermore, the present tool allowed the authors to construct a membrane protein (B2R)-based fluorescent biosensor, the fluorescence of which is enhanced (tuned on) in response to the antagonist ligand binding. The biosensor should be applicable to rapid and quant. screening and assay of potent drug candidates in the cellular context. The design concept of the affinity-guided, multivalent catalysts should facilitate further development of diverse catalyst-based protein modification tools, providing new opportunities for org. chem. in biol. research.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXptVSksLs%253D&md5=870e8766a9ab6216298c91a01586e022
(k) Tsukiji, S.; Miyagawa, M.; Takaoka, Y.; Tamura, T.; Hamachi, I. Nat. Chem. Biol. 2009, 5, 341
[ Crossref], [ PubMed], [ CAS], Google Scholar
89k
Ligand-directed tosyl chemistry for protein labeling in vivo
Tsukiji, Shinya; Miyagawa, Masayoshi; Takaoka, Yousuke; Tamura, Tomonori; Hamachi, Itaru
Nature Chemical Biology (2009), 5 (5), 341-343CODEN: NCBABT; ISSN:1552-4450. (Nature Publishing Group)
Here the authors describe a method for the site-selective attachment of synthetic mols. into specific 'endogenous' proteins in vivo using ligand-directed tosyl (LDT) chem. This approach was applied not only for chem. labeling proteins in living cells, tissues and mice but also for constructing a biosensor directly inside cells without genetic engineering. These data establish LDT chem. as a new tool for the study and manipulation of biol. systems.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXjsl2gurY%253D&md5=604943938355591f1f4f5e861c6a8278
(l) Koshi, Y.; Nakata, E.; Miyagawa, M.; Tsukiji, S.; Ogawa, T.; Hamachi, I. J. Am. Chem. Soc. 2008, 130, 245
[ ACS Full Text ], [ CAS], Google Scholar
89l
Target-Specific Chemical Acylation of Lectins by Ligand-Tethered DMAP Catalysts
Koshi, Yoichiro; Nakata, Eiji; Miyagawa, Masayoshi; Tsukiji, Shinya; Ogawa, Tomohisa; Hamachi, Itaru
Journal of the American Chemical Society (2008), 130 (1), 245-251CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
Because sugar-binding proteins, so-called lectins, play important roles in many biol. phenomena, the lectin-selective labeling should be useful for investigating biol. processes involving lectins as well as providing mol. tools for anal. of saccharides and these derivs. The authors describe herein a new strategy for lectin-selective labeling based on an acyl transfer reaction directed by ligand-tethered DMAP (4-dimethylaminopyridine). DMAP is an effective acyl transfer catalyst, which can activate an acyl ester for its transfer to a nucleophilic residue. To direct the acyl transfer reaction to a lectin of interest, the authors attached the DMAP to a saccharide ligand specific for the target lectin. It was clearly demonstrated by biochem. analyses that the target-selective labeling of Congerin II, an animal lectin having selective affinity for Lactose/LacNAc (N-acetyllactosamine), was achieved in the presence of Lac-tethered DMAPs and acyl donors contg. probes such as fluorescent mols. or biotin. Conventional peptide mapping expts. using HPLC and tandem mass-mass anal. revealed that the acyl transfer reaction site-specifically occurred at Tyr 51 of Cong II. This strategy was successfully extended to other lectins by changing the ligand part of the ligand-tethered DMAP. The authors also demonstrated that this labeling method is applicable not only to purified lectin in test tubes, but also to crude mixts. such as E. coli lysates or homogenized animal tissue samples expressing Congerin.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXhsVWqsLrK&md5=6e4b0361d59a53f2fef1724f78091821
90
Lodge, J. M.; Justin Rettenmaier, T.; Wells, J. A.; Pomerantz, W. C.; Mapp, A. K. MedChemComm 2014, 5, 370
[ Crossref], [ CAS], Google Scholar
90
FP tethering: a screening technique to rapidly identify compounds that disrupt protein-protein interactions
Lodge, Jean M.; Justin Rettenmaier, T.; Wells, James A.; Pomerantz, William C.; Mapp, Anna K.
MedChemComm (2014), 5 (3), 370-375CODEN: MCCEAY; ISSN:2040-2503. (Royal Society of Chemistry)
Tethering is a screening technique for discovering small-mol. fragments that bind to pre-detd. sites via formation of a disulfide bond. Tethering screens traditionally rely upon mass spectrometry to detect disulfide bond formation, which requires a time-consuming liq. chromatog. step. Here we show that tethering can be performed rapidly and inexpensively using a homogenous fluorescence polarization (FP) assay that detects displacement of a peptide ligand from the protein target as an indirect readout of disulfide formation. We apply this method, termed FP tethering, to identify fragments that disrupt the protein-protein interaction between the KIX domain of the transcriptional coactivator CBP and the transcriptional activator peptide pKID.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXjt1ymtbs%253D&md5=96da00435d8e4d5d16e53e7c67e7b41c
91
Sato, S.; Nakamura, H. Angew. Chem., Int. Ed. 2013, 52, 8681
[ Crossref], [ PubMed], [ CAS], Google Scholar
91
Ligand-Directed Selective Protein Modification Based on Local Single-Electron Transfer Catalysis
Sato, Shinichi; Nakamura, Hiroyuki
Angewandte Chemie, International Edition (2013), 52 (33), 8681-8684CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
A photocatalyst ([Ru(bpy)3]2+) bound to a protein ligand was essential for the title method. Local single-electron transfer from the catalyst resulted in the formation of tyrosyl radicals. N'-Acetyl-N,N-dimethyl-1,4-phenylenediamine was used as the tyrosyl radical trapping agent and used in a radical addn. to afford selective modification of the target protein.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtVGrtrzK&md5=d72e4e5fc6db1c3da367a97a31563b2b
92
Brocchini, S.; Godwin, A.; Balan, S.; Choi, J.-W.; Zloh, M.; Shaunak, S. Adv. Drug Delivery Rev. 2008, 60, 3
[ Crossref], [ PubMed], [ CAS], Google Scholar
92
Disulfide bridge based PEGylation of proteins
Brocchini, Steve; Godwin, Antony; Balan, Sibu; Choi, Ji-won; Zloh, Mire; Shaunak, Sunil
Advanced Drug Delivery Reviews (2008), 60 (1), 3-12CODEN: ADDREP; ISSN:0169-409X. (Elsevier B.V.)
A review. PEGylation is a clin. proven strategy for increasing the therapeutic efficacy of protein-based medicines. Our approach to site-specific PEGylation exploits the thiol selective chem. of the two cysteine sulfur atoms from an accessible disulfide. It involves two key steps: (1) disulfide redn. to release the two cystine thiols, and (2) bis-alkylation to give a three-carbon bridge to which PEG is covalently attached. During this process, irreversible denaturation of the protein does not occur. Mechanistically, the conjugation is conducted by a sequential, interactive bis-alkylation using α,β-unsatd.-β'-mono-sulfone functionalized PEG reagents. The combination of: - (a) maintaining the protein's tertiary structure after redn. of a disulfide, (b) bis-thiol selectivity of the PEG reagent, and (c) PEG assocd. steric shielding ensure that only one PEG mol. is conjugated at each disulfide. Our studies have shown that peptides, proteins, enzymes and antibody fragments can be site-specifically PEGylated using a native and accessible disulfide without destroying the mols.' tertiary structure or abolishing its biol. activity. As the stoichiometric efficiency of our approach also enables recycling of any unreacted protein, it offers the potential to make PEGylated biopharmaceuticals as cost-effective medicines.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXhtlyit7vP&md5=7b88a509897ed35ab3a8cc1b1609f271
93
(a) Badescu, G.; Bryant, P.; Bird, M.; Henseleit, K.; Swierkosz, J.; Parekh, V.; Tommasi, R.; Pawlisz, E.; Jurlewicz, K.; Farys, M.; Camper, N.; Sheng, X.; Fisher, M.; Grygorash, R.; Kyle, A.; Abhilash, A.; Frigerio, M.; Edwards, J.; Godwin, A. Bioconjugate Chem. 2014, 25, 1124
[ ACS Full Text ], [ CAS], Google Scholar
93a
Bridging Disulfides for Stable and Defined Antibody Drug Conjugates
Badescu, George; Bryant, Penny; Bird, Matthew; Henseleit, Korinna; Swierkosz, Julia; Parekh, Vimal; Tommasi, Rita; Pawlisz, Estera; Jurlewicz, Kosma; Farys, Monika; Camper, Nicolas; Sheng, XiaoBo; Fisher, Martin; Grygorash, Ruslan; Kyle, Andrew; Abhilash, Amrita; Frigerio, Mark; Edwards, Jeff; Godwin, Antony
Bioconjugate Chemistry (2014), 25 (6), 1124-1136CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
To improve both the homogeneity and the stability of ADCs, we have developed site-specific drug-conjugating reagents that covalently rebridge reduced disulfide bonds. The new reagents comprise a drug, a linker, and a bis-reactive conjugating moiety that is capable of undergoing reaction with both sulfur atoms derived from a reduced disulfide bond in antibodies and antibody fragments. A disulfide rebridging reagent comprising monomethyl auristatin E (MMAE) was prepd. and conjugated to trastuzumab (TRA). A 78% conversion of antibody to ADC with a drug to antibody ratio (DAR) of 4 was achieved with no unconjugated antibody remaining. The MMAE rebridging reagent was also conjugated to the interchain disulfide of a Fab derived from proteolytic digestion of TRA, to give a homogeneous single drug conjugated product. The resulting conjugates retained antigen-binding, were stable in serum, and demonstrated potent and antigen-selective cell killing in in vitro and in vivo cancer models. Disulfide rebridging conjugation is a general approach to prep. stable ADCs, which does not require the antibody to be recombinantly re-engineered for site-specific conjugation.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXntlGisr4%253D&md5=24c6fcdb6aafa32b28f3b269e04f580c
(b) Wang, T.; Ng, D. Y. W.; Wu, Y.; Thomas, J.; TamTran, T.; Weil, T. Chem. Commun. 2014, 50, 1116
[ Crossref], [ PubMed], [ CAS], Google Scholar
93b
Bis-sulfide bioconjugates for glutathione triggered tumor responsive drug release
Wang, Tao; Ng, David Y. W.; Wu, Yuzhou; Thomas, Jessica; TamTran, Thuy; Weil, Tanja
Chemical Communications (Cambridge, United Kingdom) (2014), 50 (9), 1116-1118CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
The reaction of bis-sulfone conjugation reagents with disulfide bonds allows the site-specific modification of various peptides and proteins. Herein, we present the intracellular disintegration of bis-sulfide contg. somatostatin bioconjugates under controlled, tumor-relevant glutathione levels. GSH responsive release is demonstrated, which offers high potential for designing tumor responsive therapeutics.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhvFyrt7bO&md5=4745ae77e2a6c6e915b5688a85e5eb12
(c) Wang, T.; Wu, Y.; Kuan, S. L.; Dumele, O.; Lamla, M.; Ng, D. Y. W.; Arzt, M.; Thomas, J.; Mueller, J. O.; Barner-Kowollik, C.; Weil, T. Chem.—Eur. J. 2015, 21, 228
[ Crossref], [ PubMed], [ CAS], Google Scholar
93c
A Disulfide Intercalator Toolbox for the Site-Directed Modification of Polypeptides
Wang, Tao; Wu, Yuzhou; Kuan, Seah Ling; Dumele, Oliver; Lamla, Markus; Ng, David Y. W.; Arzt, Matthias; Thomas, Jessica; Mueller, Jan O.; Barner-Kowollik, Christopher; Weil, Tanja
Chemistry - A European Journal (2015), 21 (1), 228-238CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)
A disulfide intercalator toolbox was developed for site-specific attachment of a broad variety of functional groups to proteins or peptides under mild, physiol. conditions. The peptide hormone somatostatin (SST) served as model compd. for intercalation into the available disulfide functionalization schemes starting from the intercalator or the reactive SST precursor before or after bioconjugation. A tetrazole-SST deriv. was obtained that undergoes photoinduced cycloaddn. in mammalian cells, which was monitored by live-cell imaging.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXitFamsLjN&md5=d0e7ecbf8da12acdaeaf23c412121045
94
Cong, Y.; Pawlisz, E.; Bryant, P.; Balan, S.; Laurine, E.; Tommasi, R.; Singh, R.; Dubey, S.; Peciak, K.; Bird, M.; Sivasankar, A.; Swierkosz, J.; Muroni, M.; Heidelberger, S.; Farys, M.; Khayrzad, F.; Edwards, J.; Badescu, G.; Hodgson, I.; Heise, C.; Somavarapu, S.; Liddell, J.; Powell, K.; Zloh, M.; Choi, J.-W.; Godwin, A.; Brocchini, S. Bioconjugate Chem. 2012, 23, 248
[ ACS Full Text ], [ CAS], Google Scholar
94
Site-Specific PEGylation at Histidine Tags
Cong, Yuehua; Pawlisz, Estera; Bryant, Penny; Balan, Sibu; Laurine, Emmanuelle; Tommasi, Rita; Singh, Ruchi; Dubey, Sitara; Peciak, Karolina; Bird, Matthew; Sivasankar, Amrita; Swierkosz, Julia; Muroni, Maurizio; Heidelberger, Sibylle; Farys, Monika; Khayrzad, Farzad; Edwards, Jeff; Badescu, George; Hodgson, Ian; Heise, Charles; Somavarapu, Satyanarayana; Liddell, John; Powell, Keith; Zloh, Mire; Choi, Ji-won; Godwin, Antony; Brocchini, Steve
Bioconjugate Chemistry (2012), 23 (2), 248-263CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
The efficacy of protein-based medicines can be compromised by their rapid clearance from the blood circulatory system. Achieving optimal pharmacokinetics is a key requirement for the successful development of safe protein-based medicines. Protein PEGylation is a clin. proven strategy to increase the circulation half-life of protein-based medicines. One limitation of PEGylation is that there are few strategies that achieve site-specific conjugation of PEG to the protein. Here, we describe the covalent conjugation of PEG site-specifically to a polyhistidine tag (His-tag) on a protein. His-tag site-specific PEGylation was achieved with a domain antibody (dAb) that had a 6-histidine His-tag on the C-terminus (dAb-His6) and interferon α-2a (IFN) that had an 8-histidine His-tag on the N-terminus (His8-IFN). The site of PEGylation at the His-tag for both dAb-His6-PEG and PEG-His8-IFN was confirmed by digestion, chromatog., and mass-spectral studies. A methionine was also inserted directly after the N-terminal His-tag in IFN to give His8Met-IFN. Cyanogen bromide digestion studies of PEG-His8Met-IFN were also consistent with PEGylation at the His-tag. By using increased stoichiometries of the PEGylation reagent, it was possible to conjugate two sep. PEG mols. to the His-tag of both the dAb and IFN proteins. Stability studies followed by in vitro evaluation confirmed that these PEGylated proteins retained their biol. activity. In vivo PK studies showed that all of the His-tag PEGylated samples displayed extended circulation half-lives. Together, our results indicate that site-specific, covalent PEG conjugation at a His-tag can be achieved and biol. activity maintained with therapeutically relevant proteins.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xntlanuw%253D%253D&md5=fbd2c318cfd7a5c0c91384d229044e1d
95
(a) Bryden, F.; Maruani, A.; Savoie, H.; Chudasama, V.; Smith, M. E. B.; Caddick, S.; Boyle, R. W. Bioconjugate Chem. 2014, 25, 611
[ ACS Full Text ], [ CAS], Google Scholar
95a
Regioselective and Stoichiometrically Controlled Conjugation of Photodynamic Sensitizers to a HER2 Targeting Antibody Fragment
Bryden, Francesca; Maruani, Antoine; Savoie, Huguette; Chudasama, Vijay; Smith, Mark E. B.; Caddick, Stephen; Boyle, Ross W.
Bioconjugate Chemistry (2014), 25 (3), 611-617CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
The rapidly increasing interest in the synthesis of antibody-drug conjugates as powerful targeted anticancer agents demonstrates the growing appreciation of the power of antibodies and antibody fragments as highly selective targeting moieties. This targeting ability is of particular interest in the area of photodynamic therapy, as the applicability of current clin. photosensitizers is limited by their relatively poor accumulation in target tissue in comparison to healthy tissue. Although synthesis of porphyrin-antibody conjugates has been previously demonstrated, existing work in this area has been hindered by the limitations of conventional antibody conjugation methods. This work describes the attachment of azide-functionalized, water-sol. porphyrins to a trastuzumab Fab fragment via a novel conjugation methodol. This method allows for the synthesis of a homogeneous product without the loss of structural stability assocd. with conventional methods of disulfide modification. Biol. evaluation of the synthesized conjugates demonstrates excellent selectivity for a HER2 pos. cell line over the control, with no dark toxicity obsd. in either case.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXivFOgsb4%253D&md5=d7ba37c879f3c6b087012d724fa784f1
(b) Jones, M. W.; Strickland, R. A.; Schumacher, F. F.; Caddick, S.; Baker, J. R.; Gibson, M. I.; Haddleton, D. M. J. Am. Chem. Soc. 2012, 134, 1847
[ ACS Full Text ], [ CAS], Google Scholar
95b
Polymeric Dibromomaleimides As Extremely Efficient Disulfide Bridging Bioconjugation and Pegylation Agents
Jones, Mathew W.; Strickland, Rachel A.; Schumacher, Felix F.; Caddick, Stephen; Baker, James. R.; Gibson, Matthew I.; Haddleton, David M.
Journal of the American Chemical Society (2012), 134 (3), 1847-1852CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
A series of dibromomaleimides are very efficacious at insertion into peptidic disulfide bonds. This conjugation proceeds with a stoichiometric balance of reagents in buffered solns. in <15 min to give discrete products while maintaining the disulfide bridge and thus peptide conformation. The insertion is initiated by disulfide redn. using a water-sol. phosphine, tris(2-carboxyethyl)phosphine (TCEP) which allows for subsequent substitution of the two maleimide bromides by the generated thiols. Reaction of salmon calcitonin (sCT) with 2,3-dibromomaleimide (1.1 excess) in the presence of TCEP (1.1 equiv) in aq. soln. at pH 6.2 gives complete prodn. of a single conjugate which requires no workup. A linear methoxy poly(ethylene glycol) (PEG) was functionalized via a Mitsunobu reaction and used for the successful site-specific and rapid pegylation of sCT. This reaction occurs in 15 min with a small stoichiometry excess of the pegylating agent to give insertion at the disulfide with HPLC showing a single product and MALDI-ToF confirming conjugation. Attempts to use the group in a functional ATRP polymn. initiator led to polymn. inhibition. Thus, to prep. a range of functional polymers, an indirect route was chosen via both azide and aniline functional initiators which were converted to 2,3-dibromomaleimides via appropriate reactions. For example, the azide functional polymer was reacted via a Huisgen CuAAC click reaction to an alkyne functional 2,3-dibromomaleimide. This new reagent allowed for the synthesis of conjugates of sCT with comb polymers derived from PEG methacrylic monomers which in addn. gave appropriate cloud points. This reaction represents a highly efficient polymer conjugation method which circumvents problems of purifn. which normally arise from having to use large excesses of the conjugate. In addn., the tertiary structure of the peptide is efficiently maintained.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhs1CrsLnI&md5=d25a6e0952cbd96ed1a013c1057873b1
96
(a) Jones, M. W.; Strickland, R. A.; Schumacher, F. F.; Caddick, S.; Baker, J. R.; Gibson, M. I.; Haddleton, D. M. Chem. Commun. 2012, 48, 4064
[ Crossref], [ PubMed], [ CAS], Google Scholar
96a
Highly efficient disulfide bridging polymers for bioconjugates from radical-compatible dithiophenol maleimides
Jones, Mathew W.; Strickland, Rachel A.; Schumacher, Felix F.; Caddick, Stephen; Baker, James. R.; Gibson, Matthew I.; Haddleton, David M.
Chemical Communications (Cambridge, United Kingdom) (2012), 48 (34), 4064-4066CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
The direct synthesis of dithiophenol maleimide functional polymers by living radical polymn. is described without the need for protecting group chem. The synthesized polymers have been successfully employed as disulfide bridging agents for salmon calcitonin when used in equimolar quantities, negating the requirement for complex purifn. strategies, traditionally assocd. with peptide bioconjugation.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xks1Olsrs%253D&md5=3676280121fa2cffb286523d982cc227
(b) Schumacher, F. F.; Nunes, J. P. M.; Maruani, A.; Chudasama, V.; Smith, M. E. B.; Chester, K. A.; Baker, J. R.; Caddick, S. Org. Biomol. Chem. 2014, 12, 7261
[ Crossref], [ PubMed], [ CAS], Google Scholar
96b
Next generation maleimides enable the controlled assembly of antibody-drug conjugates via native disulfide bond bridging
Schumacher, Felix F.; Nunes, Joao P. M.; Maruani, Antoine; Chudasama, Vijay; Smith, Mark E. B.; Chester, Kerry A.; Baker, James R.; Caddick, Stephen
Organic & Biomolecular Chemistry (2014), 12 (37), 7261-7269CODEN: OBCRAK; ISSN:1477-0520. (Royal Society of Chemistry)
The advent of Adcetris and Kadcyla, two recently FDA-approved antibody-drug conjugates (ADCs), in the clinic has had a major impact on the treatment of lymphoma and breast cancer patients, resp., worldwide. Despite these successes many new ADCs fail at various stages of development, often due to shortcomings in the methods used for their assembly. To address this problem we have developed next generation maleimides (NGMs), which specifically re-bridge reduced interchain disulfide bonds and allow the efficient conjugation of small mols. to antibodies, without the need for engineering of the target antibody. The method is site-specific and generates near homogeneous products in good yields. Moreover, adjustment of the reaction conditions allows control of the conjugation in terms of stoichiometry (drug-loading) and site selectivity. Using this method we prepd. a series of ADCs from trastuzumab and doxorubicin (DOX) with a controlled drug-to-antibody ratio (DAR) of 1, 2, 3 and 4. All of these constructs were fully active by ELISA and had more than 90% of re-bridged disulfide bonds by CE-SDS when compared to clin. grade antibody. Furthermore, digest expts. of the DAR 2 material revealed that almost all of the drug had been targeted to the Fab arms of the antibody. Thus, NGMs offer a flexible and simple platform for the controlled assembly of ADCs from an antibody.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtlahtrjL&md5=7789c927968a1ea63d48cac5f5fd5836
97
Castañeda, L.; Maruani, A.; Schumacher, F. F.; Miranda, E.; Chudasama, V.; Chester, K. A.; Baker, J. R.; Smith, M. E. B.; Caddick, S. Chem. Commun. 2013, 49, 8187
[ Crossref], [ PubMed], [ CAS], Google Scholar
97
Acid-cleavable thiomaleamic acid linker for homogeneous antibody-drug conjugation
Castaneda, Lourdes; Maruani, Antoine; Schumacher, Felix F.; Miranda, Enrique; Chudasama, Vijay; Chester, Kerry A.; Baker, James R.; Smith, Mark E. B.; Caddick, Stephen
Chemical Communications (Cambridge, United Kingdom) (2013), 49 (74), 8187-8189CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
In this communication we describe a novel acid-cleavable linker strategy for antibody-drug conjugation. Functional disulfide bridging of the single interchain disulfide bond of a trastuzumab Fab fragment yields a homogeneous antibody-drug conjugate bearing a thiomaleamic acid linker. This linker is stable at physiol. pH and temp., but quant. cleaves at lysosomal pH to release the drug payload.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtlWjsrvM&md5=63dbcd8a78a7bdbb599ff1e742cb35f5
98
Hull, E. A.; Livanos, M.; Miranda, E.; Smith, M. E. B.; Chester, K. A.; Baker, J. R. Bioconjugate Chem. 2014, 25, 1395
[ ACS Full Text ], [ CAS], Google Scholar
98
Homogeneous Bispecifics by Disulfide Bridging
Hull, Elizabeth A.; Livanos, Maria; Miranda, Enrique; Smith, Mark E. B.; Chester, Kerry A.; Baker, James R.
Bioconjugate Chemistry (2014), 25 (8), 1395-1401CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
We report on a chem. platform to generate site-specific, homogeneous, antibody-antibody conjugates by targeting and bridging disulfide bonds. A bispecific antibody construct was produced in good yield through simple redn. and bridging of antibody fragment disulfide bonds, using a readily synthesized bis-dibromomaleimide cross-linker. Binding activity of antibodies was maintained, and in vitro binding of target antigens was obsd. This technol. is demonstrated through linking scFv and Fab antibody fragments, showing its potential for the construction of a diverse range of bispecifics.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtFOhu7%252FK&md5=764f9e1917af2387525b5244cedc6a2d
99
(a) Dhal, P. K.; Polomoscanik, S. C.; Gianolio, D. A.; Starremans, P. G.; Busch, M.; Alving, K.; Chen, B.; Miller, R. J. Bioconjugate Chem. 2013, 24, 865
[ ACS Full Text ], [ CAS], Google Scholar
99a
Well-Defined Aminooxy Terminated N-(2-Hydroxypropyl) Methacrylamide Macromers for Site Specific Bioconjugation of Glycoproteins
Dhal, Pradeep K.; Polomoscanik, Steven C.; Gianolio, Diego A.; Starremans, Patrick G.; Busch, Michelle; Alving, Kim; Chen, Bo; Miller, Robert J.
Bioconjugate Chemistry (2013), 24 (6), 865-877CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
Syntheses and characterization of aminooxy terminated polymers of N-(2-hydroxypropyl) methacrylamide (HPMA) of controlled mol. wt. and narrow mol. wt. distribution are presented here. Design of a chain transfer agent (CTA) contg. N-tert-butoxycarbonyl (t-Boc) protected aminooxy group enabled us to use reversible addn.-fragmentation (RAFT) polymn. technique to polymerize the HPMA monomer. An amide bond was utilized to link the aminooxy group and the CTA through a triethylene glycol spacer. As a result, the aminooxy group is linked to the poly(HPMA) backbone through a hydrolytically stable amide bond. By varying the monomer to initiator ratios, polymers with targeted mol. wts. were obtained. The mol. wts. of the polymers were detd. by gel permeation chromatog. (GPC) and mass spectrometry (ESI and MALDI-TOF). The t-Boc protecting group was quant. removed to generate aminooxy terminated poly(HPMA) macromers. These macromers were converted to rhodamine B terminated poly(HPMA) by reacting N-hydroxysuccinimide (NHS) ester of the dye with the terminal aminooxy group to form a stable alkoxyamide bond. Utility of these dye-labeled polymers as mol. probes was evaluated by fluorescence microscopy by studying their intracellular uptake by renal epithelial cells. These aminooxy terminated poly(HPMA) were also tested as biocompatible carriers to prep. chemoselective bioconjugates of proteins using transferrin (Tf) as the protein. Oxidn. of the sialic acid side chains of Tf generated aldehyde functionalized protein that was reacted with aminooxy terminated poly(HPMA), which resulted in protein-polymer bioconjugates carrying oxime linkages. These bioconjugates were characterized by gel electrophoresis and MALDI-TOF mass spectrometry.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXmslSnu7Y%253D&md5=42b0571835fdf858f873263d03925573
(b) Zuberbühler, K.; Casi, G.; Bernardes, G. J. L.; Neri, D. Chem. Commun. 2012, 48, 7100
[ Crossref], [ PubMed], [ CAS], Google Scholar
99b
Fucose-specific conjugation of hydrazide derivatives to a vascular-targeting monoclonal antibody in IgG format
Zuberbuhler Kathrin; Casi Giulio; Bernardes Goncalo J L; Neri Dario
Chemical communications (Cambridge, England) (2012), 48 (56), 7100-2 ISSN:.
We describe a method that enables specific and efficient conjugation of hydrazide-moieties to an IgG targeting the tumor neovasculature. The resulting chemically defined, homogeneous hydrazone-linked IgG conjugates remain immunoreactive and have a half-life of approximately 18 hours at physiological pH and temperature suitable for localized delivery of toxic drugs.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC38jgsVCksQ%253D%253D&md5=0c3adabc3e3312c3c32d149c7a2adcdf
(c) Zeng, Y.; Ramya, T. N. C.; Dirksen, A.; Dawson, P. E.; Paulson, J. C. Nat. Methods 2009, 6, 207
[ Crossref], [ PubMed], [ CAS], Google Scholar
99c
High-efficiency labeling of sialylated glycoproteins on living cells
Zeng, Ying; Ramya, T. N. C.; Dirksen, Anouk; Dawson, Philip E.; Paulson, James C.
Nature Methods (2009), 6 (3), 207-209CODEN: NMAEA3; ISSN:1548-7091. (Nature Publishing Group)
The authors describe a simple method for efficiently labeling cell-surface sialic acid-contg. glycans on living animal cells. The method uses mild periodate oxidn. to generate an aldehyde on sialic acids, followed by aniline-catalyzed oxime ligation with a suitable tag. Aniline catalysis dramatically accelerates oxime ligation, allowing use of low concns. of aminooxy-biotin at neutral pH to label the majority of cell-surface sialylated glycoproteins while maintaining high cell viability.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXitFKltbw%253D&md5=810924d8945721f21b91b2f757a7fc06
(d) Zhang, H.; Li, X.-j.; Martin, D. B.; Aebersold, R. Nat. Biotechnol. 2003, 21, 660
[ Crossref], [ PubMed], [ CAS], Google Scholar
99d
Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry
Zhang, Hui; Li, Xiao-jun; Martin, Daniel B.; Aebersold, Ruedi
Nature Biotechnology (2003), 21 (6), 660-666CODEN: NABIF9; ISSN:1087-0156. (Nature Publishing Group)
Quant. proteome profiling using stable isotope protein tagging and automated tandem mass spectrometry (MS/MS) is an emerging technol. with great potential for the functional anal. of biol. systems and for the detection of clin. diagnostic or prognostic marker proteins. Owing to the enormous complexity of proteomes, their comprehensive anal. is an as-yet-unresolved tech. challenge. However, biol. or clin. important information can be obtained if specific, information-rich protein classes, or sub-proteomes, are isolated and analyzed. Glycosylation is the most common post-translational modification. Here we describe a method for the selective isolation, identification and quantification of peptides that contain N-linked carbohydrates. It is based on the conjugation of glycoproteins to a solid support using hydrazide chem., stable isotope labeling of glycopeptides and the specific release of formerly N-linked glycosylated peptides via peptide- N-glycosidase F (PNGase F). The recovered peptides are then identified and quantified by MS/MS. We applied the approach to the anal. of plasma membrane proteins and proteins contained in human blood serum.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXktFSlu7s%253D&md5=9374aa7ce1950b38ce7d1b11aaf2e0d5
100
Witus, L. S.; Netirojjanakul, C.; Palla, K. S.; Muehl, E. M.; Weng, C.-H.; Iavarone, A. T.; Francis, M. B. J. Am. Chem. Soc. 2013, 135, 17223
[ ACS Full Text ], [ CAS], Google Scholar
100
Site-Specific Protein Transamination Using N-Methylpyridinium-4-carboxaldehyde
Witus, Leah S.; Netirojjanakul, Chawita; Palla, Kanwal S.; Muehl, Ellen M.; Weng, Chih-Hisang; Iavarone, Anthony T.; Francis, Matthew B.
Journal of the American Chemical Society (2013), 135 (45), 17223-17229CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
The controlled attachment of synthetic groups to proteins is important for a no. of fields, including therapeutics, where antibody-drug conjugates are an emerging area of biol. medicines. We have previously reported a site-specific protein modification method using a transamination reaction that chemoselectively oxidizes the N-terminal amine of a polypeptide chain to a ketone or an aldehyde group. The newly introduced carbonyl can be used for conjugation to a synthetic group in one location through the formation of an oxime or a hydrazone linkage. To expand the scope of this reaction, we have used a combinatorial peptide library screening platform as a method to explore new transamination reagents while simultaneously identifying their optimal N-terminal sequences. N-Methylpyridinium-4-carboxaldehyde benzenesulfonate salt (Rapoport's salt, RS) was identified as a highly effective transamination reagent when paired with glutamate-terminal peptides and proteins. This finding establishes RS as a transamination reagent that is particularly well suited for antibody modification. Using a known therapeutic antibody, herceptin, it was demonstrated that RS can be used to modify the heavy chains of the wild-type antibody or to modify both the heavy and the light chains after N-terminal sequence mutation to add addnl. glutamate residues.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhslaksLfP&md5=d75726e44873a838e49c4efd50142a79
101
Carrico, I. S.; Carlson, B. L.; Bertozzi, C. R. Nat. Chem. Biol. 2007, 3, 321
[ Crossref], [ PubMed], [ CAS], Google Scholar
101
Introducing genetically encoded aldehydes into proteins
Carrico, Isaac S.; Carlson, Brian L.; Bertozzi, Carolyn R.
Nature Chemical Biology (2007), 3 (6), 321-322CODEN: NCBABT; ISSN:1552-4450. (Nature Publishing Group)
Methods for introducing bioorthogonal functionalities into proteins have become central to protein engineering efforts. Here the authors describe a method for the site-specific introduction of aldehyde groups into recombinant proteins using the 6-amino-acid consensus sequence recognized by the formylglycine-generating enzyme. This genetically encoded 'aldehyde tag' is no larger than a His6 tag and can be exploited for numerous protein labeling applications.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXltlOjuro%253D&md5=a4a6643365248f08987086bfaa70f589
102
El-Mahdi, O.; Melnyk, O. Bioconjugate Chem. 2013, 24, 735
[ ACS Full Text ], [ CAS], Google Scholar
102
α-Oxo Aldehyde or Glyoxylyl Group Chemistry in Peptide Bioconjugation
El-Mahdi, Ouafaa; Melnyk, Oleg
Bioconjugate Chemistry (2013), 24 (5), 735-765CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
A review. Since the 1990s, α-oxo aldehyde or glyoxylic acid chem. has inspired a vast array of synthetic tools for tailoring peptide or protein structures, for developing peptides endowed with novel physicochem. properties or biol. functions, for assembling a large diversity of bioconjugates or hybrid materials, or for designing peptide-based micro or nanosystems. This past decade, important developments have enriched the α-oxo aldehyde synthetic tool box in peptide bioconjugation chem. and explored novel applications. The aim of this review is to give a large overview of this creative field.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXls1eitL0%253D&md5=1bf0d72d592062cb749749fe0d4d0473
103
(a) Smith, E. L.; Giddens, J. P.; Iavarone, A. T.; Godula, K.; Wang, L.-X.; Bertozzi, C. R. Bioconjugate Chem. 2014, 25, 788
[ ACS Full Text ], [ CAS], Google Scholar
103a
Chemoenzymatic Fc Glycosylation via Engineered Aldehyde Tags
Smith, Elizabeth L.; Giddens, John P.; Iavarone, Anthony T.; Godula, Kamil; Wang, Lai-Xi; Bertozzi, Carolyn R.
Bioconjugate Chemistry (2014), 25 (4), 788-795CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
Glycoproteins with chem. defined glycosylation sites and structures are important biopharmaceutical targets and crit. tools for glycobiol. One approach toward constructing such mols. involves chem. glycosylation of aldehyde-tagged proteins. Here, we report the installation of a genetically encoded aldehyde tag at the internal glycosylation site of the crystallizable fragment (Fc) of IgG1. We replaced the natural Fc N-glycosylation sequon with a five amino-acid sequence that was efficiently converted by recombinant formylglycine generating enzyme in vitro, thereby introducing aldehyde groups for subsequent chem. elaboration. Oxime-linked glycoconjugates were synthesized by conjugating aminooxy N-acetylglucosamine to the modified Fc followed by enzymic transfer of complex N-glycans from corresponding glycan oxazolines by an EndoS-derived glycosynthase. In this manner we generated specific Fc glycoforms without relying on natural protein glycosylation machineries.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXktl2hsr8%253D&md5=4550a9f372542a49c48ab0260e1faef8
(b) Hudak, J. E.; Barfield, R. M.; de Hart, G. W.; Grob, P.; Nogales, E.; Bertozzi, C. R.; Rabuka, D. Angew. Chem., Int. Ed. 2012, 51, 4161
[ Crossref], [ PubMed], [ CAS], Google Scholar
103b
Synthesis of heterobifunctional protein fusions using copper-free click chemistry and the aldehyde tag
Hudak, Jason E.; Barfield, Robyn M.; de Hart, Gregory W.; Grob, Patricia; Nogales, Eva; Bertozzi, Carolyn R.; Rabuka, David
Angewandte Chemie, International Edition (2012), 51 (17), 4161-4165, S4161/1-S4161/16CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
Cu-free click chem. in conjunction with the aldehyde tag can produce protein-protein chem. conjugates of unprecedented size and complexity. The synthetic route capitalizes on small-mol. linkers that can increase reaction yields, lower the necessary reagent concns., and decrease the reaction time. The method should expand the topologies of available protein fusions and allow the exploration of alternate points of protein-protein attachment.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XjsFCqt74%253D&md5=b081b97d56b0eac40a3e2c81c61f1f56
(c) Ng, S.; Jafari, M. R.; Matochko, W. L.; Derda, R. ACS Chem. Biol. 2012, 7, 1482
[ ACS Full Text ], [ CAS], Google Scholar
103c
Quantitative Synthesis of Genetically Encoded Glycopeptide Libraries Displayed on M13 Phage
Ng, Simon; Jafari, Mohammad R.; Matochko, Wadim L.; Derda, Ratmir
ACS Chemical Biology (2012), 7 (9), 1482-1487CODEN: ACBCCT; ISSN:1554-8929. (American Chemical Society)
Phage display is a powerful technol. that enables the discovery of peptide ligands for many targets. Chem. modification of phage libraries have allowed the identification of ligands with properties not encountered in natural polypeptides. In this report, we demonstrated the synthesis of 2 × 108 genetically encoded glycopeptides from a com. available phage-displayed peptide library (Ph.D.-7) in a two-step, one-pot reaction in <1.5 h. Unlike previous reports, we bypassed genetic engineering of phage. The glycan moiety was introduced via an oxime ligation following oxidn. of an N-terminal Ser/Thr; these residues are present in the peptide libraries at 20-30% abundance. The construction of libraries was facilitated by simple characterization, which directly assessed the yield and regioselectivity of chem. reactions performed on phage. This quantification method also allowed facile yield detn. of reactions in 109 distinct mols. We envision that the methodol. described herein will find broad application in the synthesis of custom chem. modified phage libraries.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XptVWmsrc%253D&md5=012c744473e9f076da1f7df02e490b5c
(d) Kularatne, S. A.; Deshmukh, V.; Ma, J.; Tardif, V.; Lim, R. K. V.; Pugh, H. M.; Sun, Y.; Manibusan, A.; Sellers, A. J.; Barnett, R. S.; Srinagesh, S.; Forsyth, J. S.; Hassenpflug, W.; Tian, F.; Javahishvili, T.; Felding-Habermann, B.; Lawson, B. R.; Kazane, S. A.; Schultz, P. G. Angew. Chem., Int. Ed. 2014, 53, 11863
[ Crossref], [ PubMed], [ CAS], Google Scholar
103d
A CXCR4-Targeted Site-Specific Antibody-Drug Conjugate
Kularatne, Sumith A.; Deshmukh, Vishal; Ma, Jennifer; Tardif, Virginie; Lim, Reyna K. V.; Pugh, Holly M.; Sun, Ying; Manibusan, Anthony; Sellers, Aaron J.; Barnett, Richard S.; Srinagesh, Shailaja; Forsyth, Jane S.; Hassenpflug, Wolf; Tian, Feng; Javahishvili, Tsotne; Felding-Habermann, Brunhilde; Lawson, Brian R.; Kazane, Stephanie A.; Schultz, Peter G.
Angewandte Chemie, International Edition (2014), 53 (44), 11863-11867CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
A chem. defined anti-CXCR4-auristatin antibody-drug conjugate (ADC) was synthesized that selectively eliminates tumor cells overexpressing the CXCR4 receptor. The unnatural amino acid p-acetylphenylalanine (pAcF) was site-specifically incorporated into an anti-CXCR4 IgG and conjugated to an auristatin through a stable, noncleavable oxime linkage to afford a chem. homogeneous ADC. The full-length anti-CXCR4 ADC was selectively cytotoxic to CXCR4+ cancer cells in vitro (half maximal effective concn. (EC50)≈80-100 pM). Moreover, the anti-CXCR4 ADC eliminated pulmonary lesions from human osteosarcoma cells in a lung-seeding tumor model in mice. No significant overt toxicity was obsd. but there was a modest decrease in the bone-marrow-derived CXCR4+ cell population. Because CXCR4 is highly expressed in a majority of metastatic cancers, a CXCR4-auristatin ADC may be useful for the treatment of a variety of metastatic malignancies.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsFamu7rE&md5=30c4a48be95ebf4d797792281f4badf0
104
(a) Lu, Y.; Ngo Ndjock Mbong, G.; Liu, P.; Chan, C.; Cai, Z.; Weinrich, D.; Boyle, A. J.; Reilly, R. M.; Winnik, M. A. Biomacromolecules 2014, 15, 2027
[ ACS Full Text ], [ CAS], Google Scholar
104a
Synthesis of Polyglutamide-Based Metal-Chelating Polymers and Their Site-Specific Conjugation to Trastuzumab for Auger Electron Radioimmunotherapy
Lu, Yijie; Mbong, Ghislaine Ngo Ndjock; Liu, Peng; Chan, Conrad; Cai, Zhongli; Weinrich, Dirk; Reilly, Raymond M.; Winnik, Mitchell A.
Biomacromolecules (2014), 15 (6), 2027-2037CODEN: BOMAF6; ISSN:1525-7797. (American Chemical Society)
Three types of metal-chelating polymers (MCPs) with hydrazide end groups were synthesized. (1) The first set of polymers (the F-series) was synthesized with a furan end group, and all of the pendant groups along the chain carried only a diethylenetriaminepentaacetic acid (DTPA) metal-chelating functionality. The hydrazide was introduced via a Diels-Alder reaction between the furan and 3,3'-N-[ε-maleimidocaproic acid] hydrazide (EMCH). (2) The P-series polymers was designed to carry several copies of a nuclear-localization peptide sequence (NLS peptides, CGYGPKKKRKVGG, harboring the NLS from the simian virus 40 large T-antigen) in addn. to the DTPA metal-chelating groups. (3) The third type of polymer (the P-Py series) was a variation of the P-series polymers but with the introduction of a small no. of pyrene chromophores along the backbone to allow for UV measurement of the incorporation of the MCPs into trastuzumab (tmab). These hydrazide-terminated polymers were site-specifically conjugated to aldehyde groups generated by NaIO4 oxidn. of the pendant glycan in the Fc domain of tmab. The immunoconjugates were radiolabeled with 111In and analyzed by SE-HPLC to confirm the attachment of the polymer to the antibody. HER2 binding assays demonstrated that neither the MCPs nor the presence of the NLS peptides interfered with specific antigen recognition on SK-Br-3 cells, although nonspecific binding was increased by polymer conjugation. Our results suggest that MCPs can be site-specifically attached to antibodies via oxidized glycans in the Fc domain and labeled with 111In to construct radioimmunoconjugates with preserved immunoreactivity.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXotFCksLg%253D&md5=ab38eb6b3eefb6264cdff9ce54529ddc
(b) Zhou, Z.; Zhang, J.; Sun, L.; Ma, G.; Su, Z. Bioconjugate Chem. 2013, 25, 138
[ ACS Full Text ], Google Scholar
There is no corresponding record for this reference.
105
Kitov, P. I.; Vinals, D. F.; Ng, S.; Tjhung, K. F.; Derda, R. J. Am. Chem. Soc. 2014, 136, 8149
[ ACS Full Text ], [ CAS], Google Scholar
105
Rapid, Hydrolytically Stable Modification of Aldehyde-Terminated Proteins and Phage Libraries
Kitov, Pavel I.; Vinals, Daniel F.; Ng, Simon; Tjhung, Katrina F.; Derda, Ratmir
Journal of the American Chemical Society (2014), 136 (23), 8149-8152CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
The authors describe the rapid reaction of 2-amino benzamidoxime (ABAO) derivs. with aldehydes in water. The ABAO combines an aniline moiety for iminium-based activation of the aldehyde and a nucleophilic group (Nu:) ortho to the amine for intramol. ring closure. The reaction between ABAO and aldehydes is kinetically similar to oxime formations performed under stoichiometric aniline catalysis. The authors characterized the reaction by both NMR and UV spectroscopy and detd. that the rate-detg. step of the process is formation of a Schiff base, which is followed by rapid intramol. ring closure. The relation between apparent rate const. and pH suggests that a protonated benzamidoxime acts as an internal general acid in Schiff-base formation. The reaction is accelerated by substituents in the arom. ring that increase the basicity of the arom. amine. The rate of up to 40 M-1s-1 between an electron-rich aldehyde and 5-methoxy-ABAO (PMA), which was obsd. at pH 4.5, places this reaction among the fastest known bio-orthogonal reactions. Reaction between M13 phage-displayed library of peptides terminated with an aldehyde moiety and 1 mM biotin-ABAO deriv. reaches completion in 1 h at pH 4.5. Finally, the product of reaction, dihydroquinazoline deriv., shows fluorescence at 490 nm suggesting a possibility of developing fluorogenic aldehyde-reactive probes based on ABAO framework.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXosVOgu78%253D&md5=a63e11d567c40404430d58ba793f472a
106
Agarwal, P.; van der Weijden, J.; Sletten, E. M.; Rabuka, D.; Bertozzi, C. R. Proc. Natl. Acad. Sci. U. S. A. 2013, 110, 46
[ Crossref], [ PubMed], [ CAS], Google Scholar
106
A Pictet-Spengler ligation for protein chemical modification
Agarwal Paresh; van der Weijden Joep; Sletten Ellen M; Rabuka David; Bertozzi Carolyn R
Proceedings of the National Academy of Sciences of the United States of America (2013), 110 (1), 46-51 ISSN:.
Aldehyde- and ketone-functionalized proteins are appealing substrates for the development of chemically modified biotherapeutics and protein-based materials. Their reactive carbonyl groups are typically conjugated with α-effect nucleophiles, such as substituted hydrazines and alkoxyamines, to generate hydrazones and oximes, respectively. However, the resulting C=N linkages are susceptible to hydrolysis under physiologically relevant conditions, which limits the utility of such conjugates in biological systems. Here we introduce a Pictet-Spengler ligation that is based on the classic Pictet-Spengler reaction of aldehydes and tryptamine nucleophiles. The ligation exploits the bioorthogonal reaction of aldehydes and alkoxyamines to form an intermediate oxyiminium ion; this intermediate undergoes intramolecular C-C bond formation with an indole nucleophile to form an oxacarboline product that is hydrolytically stable. We used the reaction for site-specific chemical modification of glyoxyl- and formylglycine-functionalized proteins, including an aldehyde-tagged variant of the therapeutic monoclonal antibody Herceptin. In conjunction with techniques for site-specific introduction of aldehydes into proteins, the Pictet-Spengler ligation offers a means to generate stable bioconjugates for medical and materials applications.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3s3hslKruw%253D%253D&md5=17780fe48052ef11b12ef85f357bfa2d
107
Agarwal, P.; Kudirka, R.; Albers, A. E.; Barfield, R. M.; de Hart, G. W.; Drake, P. M.; Jones, L. C.; Rabuka, D. Bioconjugate Chem. 2013, 24, 846
[ ACS Full Text ], [ CAS], Google Scholar
107
Hydrazino-Pictet-Spengler Ligation as a Biocompatible Method for the Generation of Stable Protein Conjugates
Agarwal, Paresh; Kudirka, Romas; Albers, Aaron E.; Barfield, Robyn M.; de Hart, Gregory W.; Drake, Penelope M.; Jones, Lesley C.; Rabuka, David
Bioconjugate Chemistry (2013), 24 (6), 846-851CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
Aldehyde- and ketone-functionalized biomols. have found widespread use in biochem. and biotechnol. fields. They are typically conjugated with hydrazide or aminooxy nucleophiles under acidic conditions to yield hydrazone or oxime products that are relatively stable, but susceptible to hydrolysis over time. The authors introduce a new reaction, the hydrazino-Pictet-Spengler (HIPS) ligation, which has two distinct advantages over hydrazone and oxime ligations. First, the HIPS ligation proceeds quickly near neutral pH, allowing for one-step labeling of aldehyde-functionalized proteins under mild conditions. Second, the HIPS ligation product is very stable (>5 days) in human plasma relative to an oxime-linked conjugate (∼1 day), as demonstrated by monitoring protein-fluorophore conjugates by ELISA. Thus, the HIPS ligation exhibits a combination of product stability and speed near neutral pH that is unparalleled by current carbonyl bioconjugation chemistries.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXot1GktLk%253D&md5=a65be6fe8a29a194aef2a9e97009f8cf
108
Drake, P. M.; Albers, A. E.; Baker, J.; Banas, S.; Barfield, R. M.; Bhat, A. S.; de Hart, G. W.; Garofalo, A. W.; Holder, P.; Jones, L. C.; Kudirka, R.; McFarland, J.; Zmolek, W.; Rabuka, D. Bioconjugate Chem. 2014, 25, 1331
[ ACS Full Text ], [ CAS], Google Scholar
108
Aldehyde Tag Coupled with HIPS Chemistry Enables the Production of ADCs Conjugated Site-Specifically to Different Antibody Regions with Distinct in Vivo Efficacy and PK Outcomes
Drake, Penelope M.; Albers, Aaron E.; Baker, Jeanne; Banas, Stefanie; Barfield, Robyn M.; Bhat, Abhijit S.; de Hart, Gregory W.; Garofalo, Albert W.; Holder, Patrick; Jones, Lesley C.; Kudirka, Romas; McFarland, Jesse; Zmolek, Wes; Rabuka, David
Bioconjugate Chemistry (2014), 25 (7), 1331-1341CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
It is becoming increasingly clear that site-specific conjugation offers significant advantages over conventional conjugation chemistries used to make antibody-drug conjugates (ADCs). Site-specific payload placement allows for control over both the drug-to-antibody ratio (DAR) and the conjugation site, both of which play an important role in governing the pharmacokinetics (PK), disposition, and efficacy of the ADC. In addn. to the DAR and site of conjugation, linker compn. also plays an important role in the properties of an ADC. The authors have previously reported a novel site-specific conjugation platform comprising linker payloads designed to selectively react with site-specifically engineered aldehyde tags on an antibody backbone. This chem. results in a stable C-C bond between the antibody and the cytotoxin payload, providing a uniquely stable connection with respect to the other linker chemistries used to generate ADCs. The flexibility and versatility of the aldehyde tag conjugation platform has enabled the authors to undertake a systematic evaluation of the impact of conjugation site and linker compn. on ADC properties. Here, the authors describe the prodn. and characterization of a panel of ADCs bearing the aldehyde tag at different locations on an IgG1 backbone conjugated using Hydrazino-iso-Pictet-Spengler (HIPS) chem. The authors demonstrate that in a panel of ADCs with aldehyde tags at different locations, the site of conjugation has a dramatic impact on in vivo efficacy and pharmacokinetic behavior in rodents; this advantage translates to an improved safety profile in rats as compared to a conventional lysine conjugate.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXps1Knurs%253D&md5=fb08b4277ea6d941861f1cca293b1385
109
Han, M.-J.; Xiong, D.-C.; Ye, X.-S. Chem. Commun. 2012, 48, 11079
[ Crossref], [ PubMed], [ CAS], Google Scholar
109
Enabling Wittig reaction on site-specific protein modification
Han, Ming-Jie; Xiong, De-Cai; Ye, Xin-Shan
Chemical Communications (Cambridge, United Kingdom) (2012), 48 (90), 11079-11081CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
An efficient aq. Wittig reaction was enabled on protein bioconjugation for the first time. By investigating the reaction on small mols., peptides, and proteins, a site-specific reaction targeting "aldehyde tag" was presented. A variety of functional groups could be introduced into the protein of interest.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhsFCgt7bK&md5=965ac0249813eec7ec10eac47f37c8fd
110
Lum, K. M.; Xavier, V. J.; Ong, M. J. H.; Johannes, C. W.; Chan, K.-P. Chem. Commun. 2013, 49, 11188
[ Crossref], [ PubMed], [ CAS], Google Scholar
110
Stabilized Wittig olefination for bioconjugation
Lum, Kenneth M.; Xavier, Vanessa J.; Ong, Michelle J.-H.; Johannes, Charles W.; Chan, Kok-Ping
Chemical Communications (Cambridge, United Kingdom) (2013), 49 (95), 11188-11190CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
Stabilized Wittig olefination holds great potential as a bioconjugation reaction. We demonstrate that the reaction of stabilized phosphorus ylides (or phosphonium salts) with aryl aldehydes is sufficiently robust to be used for live cell affinity isolation and fluorescence tagging of a protein, FKBP12.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhslWlsLnK&md5=bd16969717433cfb601d76a5775106b8
111
van Hest, J. C. M.; van Delft, F. L. ChemBioChem 2011, 12, 1309
[ Crossref], [ PubMed], [ CAS], Google Scholar
111
Protein Modification by Strain-Promoted Alkyne-Azide Cycloaddition
van Hest, Jan C. M.; van Delft, Floris L.
ChemBioChem (2011), 12 (9), 1309-1312CODEN: CBCHFX; ISSN:1439-4227. (Wiley-VCH Verlag GmbH & Co. KGaA)
A review. Strain-promoted reactions between cyclooctynes and 1,3-dipoles have emerged as a versatile technol. for the modification of proteins. A broad range of methods has been developed for the introduction of azides (and other dipoles) into proteins, and a range of cyclooctynes has now become synthetically readily accessible or com. available. The emergence of these techniques will greatly expand the ability to prep. homogeneous protein conjugates (PEGylation, dimerization, spin-labeling, etc.) without the need for metals or reagents; this could be of great value for, for example, the manuf. of biopharmaceuticals. The recent demonstration that cyclooctyne can be genetically encoded into a protein will facilitate the direct read-out of protein tracking in living cells and potentially whole organisms, and is therefore a substantial extension of the bioconjugation toolbox. Cycloaddns. with other, more reactive dipoles than azide (e.g., nitrones or nitrile oxides) is also feasible now. Although the reactivity of cyclooctyn-3-ol is relatively low, the genetic encoding of more reactive cyclic alkynes is a logical next step.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXnt1Krsbw%253D&md5=118ebedf36f378517c3ee6a68a15cf27
112
(a) Ahad, A. M.; Jensen, S. M.; Jewett, J. C. Org. Lett. 2013, 15, 5060
[ ACS Full Text ], [ CAS], Google Scholar
112a
A Traceless Staudinger Reagent To Deliver Diazirines
Ahad, Ali M.; Jensen, Stephanie M.; Jewett, John C.
Organic Letters (2013), 15 (19), 5060-5063CODEN: ORLEF7; ISSN:1523-7052. (American Chemical Society)
A triarylphosphine reagent that reacts with org. azides to install amide-linked diazirines is reported [e.g., Staudinger-Bertozzi ligation of PhosDAz I with benzyl azide afforded diazirine amide II in 96% yield]. This traceless Staudinger reagent reacts with complex org. azides to yield amide-linked diazirines, thus expanding the scope of the utility of both azide and diazirine chem.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhsVyrtLnI&md5=7d2eec56727a5fc61edfb92ab2504f48
(b) Bernardes, G. J. L.; Linderoth, L.; Doores, K. J.; Boutureira, O.; Davis, B. G. ChemBioChem 2011, 12, 1383
[ Crossref], [ PubMed], [ CAS], Google Scholar
112b
Site-Selective Traceless Staudinger Ligation for Glycoprotein Synthesis Reveals Scope and Limitations
Bernardes, Goncalo J. L.; Linderoth, Lars; Doores, Katie J.; Boutureira, Omar; Davis, Benjamin G.
ChemBioChem (2011), 12 (9), 1383-1386CODEN: CBCHFX; ISSN:1439-4227. (Wiley-VCH Verlag GmbH & Co. KGaA)
The Staudinger reaction is another azide-selective reaction that has been used, for example, to modify cell surface carbohydrates, and to label proteins that contain an azidohomoalanine (Aha). Here, the authors prepd. a glucosyl phosphine deriv. and coupled it with an azide protein substrate using the traceless Staudinger reaction. The azide protein was fully consumed to give equimolar amts. of ligated amide product and reduced amine product.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXnt1Krsb4%253D&md5=a3bc19e896fa00a6d5218cee1607e063
113
Serwa, R.; Majkut, P.; Horstmann, B.; Swiecicki, J.-M.; Gerrits, M.; Krause, E.; Hackenberger, C. P. R. Chem. Sci. 2010, 596
[ Crossref], [ CAS], Google Scholar
113
Site-specific PEGylation of proteins by a Staudinger-phosphite reaction
Serwa, Remigiusz; Majkut, Paul; Horstmann, Benjamin; Swiecicki, Jean-Marie; Gerrits, Michael; Krause, Eberhard; Hackenberger, Christian P. R.
Chemical Science (2010), 1 (5), 596-602CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)
Current protocols in protein bioengineering allow the site-specific incorporation of chem. reporter moieties. Subsequently, these functional groups can be chemoselectively transformed to decorate proteins with charged and oversized functional units. Based on our recent report on the chemoselective reaction of azides with phosphites, we now apply the Staudinger-phosphite reaction to an efficient and metal-free PEGylation of an azide-contg. protein with sym. phosphites. Thereby, two types of branched oligoethylene glycol scaffolds are generated, which deliver either a stable or light-cleavable protein-PEG conjugate. Furthermore, we demonstrate that the Staudinger-phosphite reaction is an efficient transformation in both aq. media as well as in a highly crowded bacterial cell lysate.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXht1OgsbjE&md5=87116fe4116df6e153a271d9d0bf0c5b
114
Vallée, M. R. J.; Majkut, P.; Wilkening, I.; Weise, C.; Müller, G.; Hackenberger, C. P. R. Org. Lett. 2011, 13, 5440
[ ACS Full Text ], [ CAS], Google Scholar
114
Staudinger-Phosphonite Reactions for the Chemoselective Transformation of Azido-Containing Peptides and Proteins
Vallee, M. Robert J.; Majkut, Paul; Wilkening, Ina; Weise, Christoph; Mueller, Gregor; Hackenberger, Christian P. R.
Organic Letters (2011), 13 (20), 5440-5443CODEN: ORLEF7; ISSN:1523-7052. (American Chemical Society)
Site-specific functionalization of proteins by bioorthogonal modification offers a convenient pathway to create, modify, and study biol. active biopolymers. In this paper the Staudinger reaction of aryl-phosphonites for the chemoselective functionalization of azido-peptides and proteins was probed. Different water-sol. phosphonites with oligoethylene substituents were synthesized and reacted with unprotected azido-contg. peptides in aq. systems at room temp. in high conversions. Finally, the Staudinger-phosphonite reaction was successfully applied to the site-specific modification of the protein calmodulin.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXht1ClsbzO&md5=c79e0fee41ef9adfddd8bfdc0d7f22f9
115
Debets, M. F.; van Berkel, S. S.; Dommerholt, J.; Dirks, A. J.; Rutjes, F. P. J. T.; van Delft, F. L. Acc. Chem. Res. 2011, 44, 805
[ ACS Full Text ], [ CAS], Google Scholar
115
Bioconjugation with Strained Alkenes and Alkynes
Debets, Marjoke F.; van Berkel, Sander S.; Dommerholt, Jan; Dirks, A. J.; Rutjes, Floris P. J. T.; van Delft, Floris L.
Accounts of Chemical Research (2011), 44 (9), 805-815CODEN: ACHRE4; ISSN:0001-4842. (American Chemical Society)
A review. The structural complexity of mols. isolated from biol. sources has always served as an inspiration for org. chemists. Since the first synthesis of a natural product, urea, chemists have been challenged to prep. exact copies of natural structures in the lab. As a result, a broad repertoire of synthetic transformations has been developed over the years. It is now feasible to synthesize org. mols. of enormous complexity, and also mols. with less structural complexity but prodigious societal impact, such as nylon, TNT, polystyrene, statins, estradiol, XTC, and many more. Unfortunately, only a few chem. transformations are so mild and precise that they can be used to selectively modify biochem. structures, such as proteins or nucleic acids; these are the so-called bioconjugation strategies. Even more challenging is to apply a chem. reaction on or in living cells or whole organisms; these are the so-called bioorthogonal reactions. These fields of research are of particular importance because they not only pose a worthy challenge for chemists but also offer unprecedented possibilities for studying biol. systems, esp. in areas in which traditional biochem. and mol. biol. tools fall short. Recent years have seen tremendous growth in the chem. biol. toolbox. In particular, a rapidly increasing no. of bioorthogonal reactions has been developed based on chem. involving strained alkenes or strained alkynes. Such strained unsatd. systems have the unique ability to undergo (3+2) and (4+2) cycloaddns. with a diverse set of complementary reaction partners. Accordingly, chem. centered around strain-promoted cycloaddns. has been exploited to precisely modify biopolymers, ranging from nucleic acids to proteins to glycans. In this Account, the authors describe progress in bioconjugation centered around cycloaddns. of these strained unsatd. systems. Being among the first to recognize the utility of strain-promoted cycloaddns. between alkenes and dipoles, the authors highlight their report in 2007 of the reaction of oxanobornadienes with azides, which occurs through a sequential cycloaddn. and retro Diels-Alder reaction. The authors further consider the subsequent refinement of this reaction as a valuable tool in chem. biol. The authors also examine the development of the reaction of cyclooctyne, the smallest isolable cyclic alkyne, with a range of substrates. Owing to severe deformation of the triple bond from ideal linear geometry, the cyclooctynes show high reactivity toward dienes, 1,3-dipoles, and other mol. systems. In the search for bioorthogonal reactions, cycloaddns. of cyclic alkenes and alkynes have now established themselves as powerful tools in reagent-free bioconjugations.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXovFKmtbw%253D&md5=458aef02c8c2d806af82d04dfd4deb22
116
(a) Li, X.; Fang, T.; Boons, G.-J. Angew. Chem., Int. Ed. 2014, 53, 7179
[ Crossref], [ PubMed], [ CAS], Google Scholar
116a
Preparation of well-defined antibody-drug conjugates through glycan remodeling and strain-promoted azide-alkyne cycloadditions
Li, Xiuru; Fang, Tao; Boons, Geert-Jan
Angewandte Chemie, International Edition (2014), 53 (28), 7179-7182CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
Antibody-drug conjugates hold considerable promise as anticancer agents, however, producing them remains a challenge and there is a need for mild, broadly applicable, site-specific conjugation methods that yield homogenous products. It was envisaged that enzymic remodeling of the oligosaccharides of an antibody would enable the introduction of reactive groups that can be exploited for the site-specific attachment of cytotoxic drugs. This is based on the observation that glycosyltransferases often tolerate chem. modifications in their sugar nucleotide substrates, thus allowing the installation of reactive functionalities. An azide was incorporated because this functional group is virtually absent in biol. systems and can be reacted by strain-promoted alkyne-azide cycloaddn. This method, which does not require genetic engineering, was used to produce an anti-CD22 antibody modified with doxorubicin to selectively target and kill lymphoma cells.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXos1aks7w%253D&md5=d59a17169fb0891a63e88960285c4f55
(b) Zeglis, B. M.; Davis, C. B.; Aggeler, R.; Kang, H. C.; Chen, A.; Agnew, B. J.; Lewis, J. S. Bioconjugate Chem. 2013, 24, 1057
[ ACS Full Text ], [ CAS], Google Scholar
116b
Enzyme-Mediated Methodology for the Site-Specific Radiolabeling of Antibodies Based on Catalyst-Free Click Chemistry
Zeglis, Brian M.; Davis, Charles B.; Aggeler, Robert; Kang, Hee Chol; Chen, Aimei; Agnew, Brian J.; Lewis, Jason S.
Bioconjugate Chemistry (2013), 24 (6), 1057-1067CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
An enzyme- and click chem.-mediated methodol. for the site-selective radiolabeling of antibodies on the heavy chain glycans has been developed and validated. To this end, a model system based on the prostate specific membrane antigen-targeting antibody J591, the positron-emitting radiometal 89Zr, and the chelator desferrioxamine has been employed. The methodol. consists of four steps: (1) the removal of sugars on the heavy chain region of the antibody to expose terminal N-acetylglucosamine residues; (2) the incorporation of azide-modified N-acetylgalactosamine monosaccharides into the glycans of the antibody; (3) the catalyst-free click conjugation of desferrioxamine-modified dibenzocyclooctynes to the azide-bearing sugars; and (4) the radiolabeling of the chelator-modified antibody with 89Zr. The site-selective labeling methodol. proved facile, reproducible, and robust, producing 89Zr-labeled radioimmunoconjugates that display high stability and immunoreactivity in vitro (>95%) in addn. to highly selective tumor uptake (67.5 ± 5.0%ID/g) and tumor-to-background contrast in athymic nude mice bearing PSMA-expressing s.c. LNCaP xenografts. Ultimately, this strategy could play a crit. role in the development of novel well-defined and highly immunoreactive radioimmunoconjugates for both the lab. and clinic.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXnvVGjs70%253D&md5=ddea6ba4b4ce68903c6829cdc2ccd6c2
(c) Zhou, Q.; Gui, J.; Pan, C.-M.; Albone, E.; Cheng, X.; Suh, E. M.; Grasso, L.; Ishihara, Y.; Baran, P. S. J. Am. Chem. Soc. 2013, 135, 12994
[ ACS Full Text ], [ CAS], Google Scholar
116c
Bioconjugation by Native Chemical Tagging of C-H Bonds
Zhou, Qianghui; Gui, Jinghan; Pan, Chung-Mao; Albone, Earl; Cheng, Xin; Suh, Edward M.; Grasso, Luigi; Ishihara, Yoshihiro; Baran, Phil S.
Journal of the American Chemical Society (2013), 135 (35), 12994-12997CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
A general C-H functionalization method for the tagging of natural products and pharmaceuticals is described. An azide-contg. sulfinate reagent allows the appendage of azidoalkyl chains onto heteroaroms., the product of which can then be attached to a monoclonal antibody by a "click" reaction. This strategy expands the breadth of bioactive small mols. that can be linked to macromols. in a manner that is beyond the scope of existing methods in bioconjugation to permit tagging of the "seemingly untaggable".
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtlSjur3P&md5=dca0179112d7d412fa38073c986a0730
117
Jang, S.; Sachin, K.; Lee, H.-j.; Kim, D. W.; Lee, H. S. Bioconjugate Chem. 2012, 23, 2256
[ ACS Full Text ], [ CAS], Google Scholar
117
Development of a Simple Method for Protein Conjugation by Copper-Free Click Reaction and Its Application to Antibody-Free Western Blot Analysis
Jang, Sohye; Sachin, Kalme; Lee, Hui-jeong; Kim, Dong Wook; Lee, Hyun Soo
Bioconjugate Chemistry (2012), 23 (11), 2256-2261CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
There are currently many methods available for labeling proteins to study their structure and function. However, the utility of these methods is hampered by low efficiency, slow reaction rates, nonbiocompatible reaction conditions, large-sized labeling groups, and the requirement of specific side chains such as cysteine or lysine. A simple and efficient method for protein labeling was developed, in which an azide-contg. amino acid was introduced into a protein and conjugated to a labeling reagent by strain-promoted azide-alkyne cycloaddn. (SPAAC). This method allowed the authors to label proteins by simply mixing a protein and a labeling reagent in physiol. conditions with a labeling yield of ∼80% in 120 min. In addn., the specificity of SPAAC made it possible to analyze the expression level of a protein quant. by simple mixing and SDS-PAGE anal. with no need for antibodies or multistep incubations. Because the genetic incorporation of the azide-contg. amino acid can be generally applied to any protein and the SPAAC reaction is highly specific, this method should prove useful for labeling and analyzing proteins.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhsVGisrnP&md5=df6852fab28fdf6dbed759991560b4c4
118
van Geel, R.; Pruijn, G. J. M.; van Delft, F. L.; Boelens, W. C. Bioconjugate Chem. 2012, 23, 392
[ ACS Full Text ], [ CAS], Google Scholar
118
Preventing Thiol-Yne Addition Improves the Specificity of Strain-Promoted Azide-Alkyne Cycloaddition
van Geel, Remon; Pruijn, Ger J. M.; van Delft, Floris L.; Boelens, Wilbert C.
Bioconjugate Chemistry (2012), 23 (3), 392-398CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
The 1,3-dipolar cycloaddn. of azides with ring-strained alkynes is one of the few bioorthogonal reactions suitable for specific biomol. labeling in complex biol. systems. Nevertheless, azide-independent labeling of proteins by strained alkynes can occur to a varying extent, thereby limiting the sensitivity of assays based on strain-promoted azide-alkyne cycloaddn. (SPAAC). A subset of three cyclooctynes, dibenzocyclooctyne (DIBO), azadibenzocyclooctyne (DIBAC), and bicyclo[6.1.0]nonyne (BCN), was used to evaluate the azide-independent labeling of proteins in vitro. For all three cyclooctynes, thiol-yne addn. with reduced peptidylcysteines is responsible for most of the azide-independent polypeptide labeling. The identity of the reaction product was confirmed by LC-MS and NMR anal. Moreover, undesired thiol-yne reactions can be prevented by alkylating peptidylcysteine thiols with iodoacetamide (IAM). Since IAM is compatible with SPAAC, a more specific azide-dependent labeling is achieved by preincubating proteins contg. reduced cysteines with IAM.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XjtVWhsL0%253D&md5=091ab818d0b4582a4377e6a6a305a598
119
Poole, T. H.; Reisz, J. A.; Zhao, W.; Poole, L. B.; Furdui, C. M.; King, S. B. J. Am. Chem. Soc. 2014, 136, 6167
[ ACS Full Text ], [ CAS], Google Scholar
119
Strained Cycloalkynes as New Protein Sulfenic Acid Traps
Poole, Thomas H.; Reisz, Julie A.; Zhao, Weiling; Poole, Leslie B.; Furdui, Cristina M.; King, S. Bruce
Journal of the American Chemical Society (2014), 136 (17), 6167-6170CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
Protein sulfenic acids are formed by the reaction of biol. relevant reactive oxygen species with protein thiols. Sulfenic acid formation modulates the function of enzymes and transcription factors either directly or through the subsequent formation of protein disulfide bonds. Identifying the site, timing, and conditions of protein sulfenic acid formation remains crucial to understanding cellular redox regulation. Current methods for trapping and analyzing sulfenic acids involve the use of dimedone and other nucleophilic 1,3-dicarbonyl probes that form covalent adducts with cysteine-derived protein sulfenic acids. As a mechanistic alternative, the present study describes highly strained bicyclo[6.1.0]nonyne (BCN) derivs. as concerted traps of sulfenic acids. These strained cycloalkynes react efficiently with sulfenic acids in proteins and small mols. yielding stable alkenyl sulfoxide products at rates >100x greater than 1,3-dicarbonyl reagents enabling kinetic competition with physiol. sulfur chem. Similar to the 1,3-dicarbonyl reagents, the BCN compds. distinguish the sulfenic acid oxoform from the thiol, disulfide, sulfinic acid, and S-nitrosated forms of cysteine while displaying an acceptable cell toxicity profile. The enhanced rates demonstrated by these strained alkynes identify them as new bioorthogonal probes that should facilitate the discovery of previously unknown sulfenic acid sites and their parent proteins.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXmtVegtL0%253D&md5=af7b13df6e6bd4101306df5be38bd88a
120
Ning, X.; Temming, R. P.; Dommerholt, J.; Guo, J.; Ania, D. B.; Debets, M. F.; Wolfert, M. A.; Boons, G.-J.; van Delft, F. L. Angew. Chem., Int. Ed. 2010, 49, 3065
[ Crossref], [ PubMed], [ CAS], Google Scholar
120
Protein Modification by Strain-Promoted Alkyne-Nitrone Cycloaddition
Ning, Xinghai; Temming, Rinske P.; Dommerholt, Jan; Guo, Jun; Ania, Daniel B.; Debets, Marjoke F.; Wolfert, Margreet A.; Boons, Geert-Jan; van Delft, Floris L.
Angewandte Chemie, International Edition (2010), 49 (17), 3065-3068, S3065/1-S3065/22CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
The authors report a novel bioorthogonal reaction pair based on strain-promoted alkyne-nitrone cycloaddn. (SPANC) to give N-alkylated isoxazolines with exceptionally fast reaction kinetics. The new methodol. was used in a one-pot three-step protocol for the site-specific modification of peptides and proteins.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXkslSjs7Y%253D&md5=effbd9191246bdeccc84d091eba02a4b
121
Colombo, M.; Sommaruga, S.; Mazzucchelli, S.; Polito, L.; Verderio, P.; Galeffi, P.; Corsi, F.; Tortora, P.; Prosperi, D. Angew. Chem., Int. Ed. 2012, 51, 496
[ Crossref], [ CAS], Google Scholar
121
Site-Specific Conjugation of ScFvs Antibodies to Nanoparticles by Bioorthogonal Strain-Promoted Alkyne-Nitrone Cycloaddition
Colombo, Miriam; Sommaruga, Silvia; Mazzucchelli, Serena; Polito, Laura; Verderio, Paolo; Galeffi, Patrizia; Corsi, Fabio; Tortora, Paolo; Prosperi, Davide
Angewandte Chemie, International Edition (2012), 51 (2), 496-499, S496/1-S496/17CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
The authors demonstrated that strain-promoted azide-nitrone cycloaddn. (SPANC) allowed for the rapid and effective conjugation of proteins on nanoparticles functionalized with cyclooctyne ligands under mild conditions, provided that an N-terminal serine residue was introduced by mol. engineering. In particular, the application of SPANC to a scFv antibody against HER2 tumor marker resulted in its prompt immobilization on multifunctional nanoparticles (MFN), leading to water-stable bioengineered targeted MFN (TMFN), which exhibited a complete conservation of protein effectiveness in selectively targeting HER2 receptor in living cells. As the structural motif of scFv fragments is highly conserved, and other kinds of nanoparticles can be modified identically with the same polymer used herein, this approach is expected to be of general utility and may become a universal strategy for the development of a new generation of targeted nanoparticles.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhsFeqt7jJ&md5=f3d248326e6a8e4535d99242e4dc8067
122
Sanders, B. C.; Friscourt, F.; Ledin, P. A.; Mbua, N. E.; Arumugam, S.; Guo, J.; Boltje, T. J.; Popik, V. V.; Boons, G.-J. J. Am. Chem. Soc. 2011, 133, 949
[ ACS Full Text ], [ CAS], Google Scholar
122
Metal-Free Sequential [3 + 2]-Dipolar Cycloadditions using Cyclooctynes and 1,3-Dipoles of Different Reactivity
Sanders, Brian C.; Friscourt, Frederic; Ledin, Petr A.; Mbua, Ngalle Eric; Arumugam, Selvanathan; Guo, Jun; Boltje, Thomas J.; Popik, Vladimir V.; Boons, Geert-Jan
Journal of the American Chemical Society (2011), 133 (4), 949-957CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
Although metal-free cycloaddns. of cyclooctynes and azides to give stable 1,2,3-triazoles have found wide utility in chem. biol. and material sciences, there is an urgent need for faster and more versatile bioorthogonal reactions. Here, it was shown that nitrile oxides and diazocarbonyl derivs. undergo facile 1,3-dipolar cycloaddns. with cyclooctynes. Cycloaddns. with diazocarbonyl derivs. exhibited similar kinetics as compared to azides, whereas the reaction rates of cycloaddns. with nitrile oxides were much faster. Nitrile oxides could conveniently be prepd. by direct oxidn. of the corresponding oximes with BAIB, and these conditions made it possible to perform oxime formation, oxidn., and cycloaddn. as a one-pot procedure. The methodol. was employed to functionalize the anomeric center of carbohydrates with various tags. Furthermore, oximes and azides provide an orthogonal pair of functional groups for sequential metal-free click reactions, and this feature makes it possible to multifunctionalize biomols. and materials by a simple synthetic procedure that does not require toxic metal catalysts.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhs1Srsb%252FL&md5=bb3c45c06a0ddd51b337e52ccf83afd3
123
Plougastel, L.; Koniev, O.; Specklin, S.; Decuypere, E.; Créminon, C.; Buisson, D.-A.; Wagner, A.; Kolodych, S.; Taran, F. Chem. Commun. 2014, 50, 9376
[ Crossref], [ PubMed], [ CAS], Google Scholar
123
4-Halogeno-sydnones for fast strain promoted cycloaddition with bicyclo-[6.1.0]-nonyne
Plougastel, Lucie; Koniev, Oleksandr; Specklin, Simon; Decuypere, Elodie; Creminon, Christophe; Buisson, David-Alexandre; Wagner, Alain; Kolodych, Sergii; Taran, Frederic
Chemical Communications (Cambridge, United Kingdom) (2014), 50 (66), 9376-9378CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
New sydnone derivs. have been synthesized and screened for their capacity to undergo fast copper-free cycloaddn. reaction with bicyclo-[6.1.0]-nonyne to produce hydroxymethyldiazatricyclododecadienes, e. g., I. The influences of substitution in positions N-3 and C-4 of sydnones have been particularly studied leading to the identification of highly reactive partners for bio-orthogonal ligation reactions.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtVOnsrzO&md5=6f9ce153d24d861f1514e398f0f1994d
124
Stöckmann, H.; Neves, A. A.; Stairs, S.; Brindle, K. M.; Leeper, F. J. Org. Biomol. Chem. 2011, 9, 7303
[ Crossref], [ PubMed], [ CAS], Google Scholar
124
Exploring isonitrile-based click chemistry for ligation with biomolecules
Stockmann Henning; Neves Andre A; Stairs Shaun; Brindle Kevin M; Leeper Finian J
Organic & biomolecular chemistry (2011), 9 (21), 7303-5 ISSN:.
We show here that isonitriles can perform click reactions with tetrazines in aqueous media, making them promising candidates for ligation reactions in chemical biology and polymer chemistry. This is the first time that a [4+1] cycloaddition has been used as a biocompatible ligation reaction.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3Mbgt1amug%253D%253D&md5=26eb8391000d79a5fef3ccabb9a91300
125
(a) Li, Y.; Pan, M.; Li, Y.; Huang, Y.; Guo, Q. Org. Biomol. Chem. 2013, 11, 2624
[ Crossref], [ PubMed], [ CAS], Google Scholar
125a
Thiol-yne radical reaction mediated site-specific protein labeling via genetic incorporation of an alkynyl-L-lysine analogue
Li, Yiming; Pan, Man; Li, Yitong; Huang, Yichao; Guo, Qingxiang
Organic & Biomolecular Chemistry (2013), 11 (16), 2624-2629CODEN: OBCRAK; ISSN:1477-0520. (Royal Society of Chemistry)
Three N(ε)-alkynyl lysine derivs., H-Lys(CO2CH2C≡CH)-OH, H-Lys(CO2CH2CH2C≡CH)-OH and H-Lys(CO2CH2CH2CH2C≡CH)-OH, were synthesized and genetically encoded into proteins by a mutant PylRS-tRNA pair with high efficiencies. With these alkyne handles, site-specific dual labeling of proteins can be achieved via a bioorthogonal thiol-yne ligation reaction.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXksF2gsbk%253D&md5=d2a50bec20554216efca3b6919628a5e
(b) Li, Y.; Yang, M.; Huang, Y.; Song, X.; Liu, L.; Chen, P. R. Chem. Sci. 2012, 3, 2766
[ Crossref], [ CAS], Google Scholar
125b
Genetically encoded alkenyl-pyrrolysine analogues for thiol-ene reaction mediated site-specific protein labeling
Li, Yiming; Yang, Maiyun; Huang, Yichao; Song, Xiaoda; Liu, Lei; Chen, Peng R.
Chemical Science (2012), 3 (9), 2766-2770CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)
A series of alkene-bearing pyrrolysine analogs were synthesized and subsequently incorporated into proteins at two sites by a mutant PylRS-tRNA pair with excellent efficiency. This strategy allowed the site-specific labeling of proteins carrying single or double genetically encoded alkene handles via bioorthogonal thiol-ene ligation reactions.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtFWns7zP&md5=ef1a6ad5a1c103b0593760d427fe9577
126
(a) Thomas, J. D.; Cui, H.; North, P. J.; Hofer, T.; Rader, C.; Burke, T. R. Bioconjugate Chem. 2012, 23, 2007
[ ACS Full Text ], [ CAS], Google Scholar
126a
Application of Strain-Promoted Azide-Alkyne Cycloaddition and Tetrazine Ligation to Targeted Fc-Drug Conjugates
Thomas, Joshua D.; Cui, Huiting; North, Patrick, J.; Hofer, Thomas; Rader, Christoph; Burke, Terrence R.
Bioconjugate Chemistry (2012), 23 (10), 2007-2013CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
We have previously described an approach whereby antibody Fc fragments harboring a single C-terminal selenocysteine residue (Fc-Sec) are directed against a variety of targets by changing the peptide or small mol. to which they are conjugated. In the present work, we describe methodol. for improving the efficacy of these Fc-Sec conjugates by incorporating cytotoxic drugs. The Fc-Sec protein is first programmed to target specific tumor cell types by attachment of a bifunctional linker that contains a "clickable" handle (e.g., cyclobutane or cyclooctyne) in addn. to a tumor cell-binding peptide or small mol. Following Fc-Sec conjugation, a cytotoxic warhead is then attached by cycloaddn. reactions of tetrazine or azide-contg. linker. To validate this approach, we used a model system in which folic acid (FA) is the targeting moiety and a disulfide-linked biotin moiety serves as a cytotoxic drug surrogate. We demonstrated successful targeting of Fc-Sec proteins to folate-receptor expressing tumor cells. Tetrazine ligation was found to be an efficient method for biotin "arming" of the folate-targeted Fc-Sec proteins. We also report novel bioconjugation methodologies that use [4 + 2] cycloaddn. reactions between tetrazines and cyclooctynes.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtlKlsbfP&md5=f6056b2a9f8ba428edd8785f95cbc2b9
(b) Kele, P.; Mezö, G.; Achatz, D.; Wolfbeis, O. S. Angew. Chem., Int. Ed. 2009, 48, 344
[ Crossref], [ PubMed], [ CAS], Google Scholar
126b
Dual labeling of biomolecules by using click chemistry: a sequential approach
Kele, Peter; Mezo, Gabor; Achatz, Daniela; Wolfdeis, Otto S.
Angewandte Chemie, International Edition (2009), 48 (2), 344-347CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
Dual labeling of model compds. was carried out by using copper-free and copper-mediated click chem. in a sequential manner. This method was used to introduce two labels onto biol. targets or nanoparticles, thus quickly converting them into fluorescence resonance energy transfer systems.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXhtFGns74%253D&md5=d831d2fd30cfbb51ff59099bc075ddab
127
(a) Plass, T.; Milles, S.; Koehler, C.; Szymański, J.; Mueller, R.; Wießler, M.; Schultz, C.; Lemke, E. A. Angew. Chem., Int. Ed. 2012, 51, 4166
[ Crossref], [ PubMed], [ CAS], Google Scholar
127a
Amino Acids for Diels-Alder Reactions in Living Cells
Plass, Tilman; Milles, Sigrid; Koehler, Christine; Szymanski, Jedrzej; Mueller, Rainer; Wiessler, Manfred; Schultz, Carsten; Lemke, Edward A.
Angewandte Chemie, International Edition (2012), 51 (17), 4166-4170, S4166/1-S4166/22CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
The authors have genetically encoded unnatural amino acids (UAAs) for a biocompatible chem. in living cells that is orthogonal to the previously described cyclooctyne azide click chem. The basic utility of this new method for labeling of proteins in vivo was demonstrated in Escherichia coli. A particular focus of future work will be the development of more hydrophilic UAAs that facilitate easy washout of unincorporated UAA and thus high-contrast imaging. However, the authors were already able to show the high potential of genetically encoding a trans-cyclooctene deriv. for fluorescence imaging of specifically labeled proteins in mammalian cell culture. This approach will pave the way for labeling single protein sites with small fluorophores and other anal. or functional labels in physiol. relevant cells in the future.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XkvVKjs7c%253D&md5=40e0fe8d46aebd25280636e43185a0ec
(b) Plass, T.; Milles, S.; Koehler, C.; Schultz, C.; Lemke, E. A. Angew. Chem., Int. Ed. 2011, 50, 3878
[ Crossref], [ PubMed], [ CAS], Google Scholar
127b
Genetically Encoded Copper-Free Click Chemistry
Plass, Tilman; Milles, Sigrid; Koehler, Christine; Schultz, Carsten; Lemke, Edward A.
Angewandte Chemie, International Edition (2011), 50 (17), 3878-3881, S3878/1-S3878/13CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
One of the most potent functional groups for in vivo chem. has been genetically encoded into E. coli, and its basic utility for in vivo labeling as well as high-resoln. single-mol. measurements has been demonstrated. SPAAC (strain-promoted azide-alkyne cycloaddn.) chem. is now available to site-specifically and noninvasively modify proteins in living cells. As the tRNA'/pylRSA showed no obvious dependence on linker length (1 vs. 2), it is conceivable that slightly altered derivs., such as mono- and difluorinated cyclooctynes, and possibly bicyclonones, could be directly used in this system. Other enhanced cyclooctynes, such as dibenzocycloctynes, could pose substantial challenges to the synthetase and/or the host translational machinery owing to their larger size. As pylRS from M. mazei is orthogonal in a variety of eukaryotic organisms, we are now evaluating the transfer of this system to mammalian cells, where the technique would not only greatly expand our abilities to track proteins in living specimen but also to introduce other type of functional groups, such as cross-linkers or spin-labels for NMR spectroscopy and magnetic resonance imaging (MRI) in living specimens.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXkslChsLk%253D&md5=778aa80f13b1ea97bfce8236adc2cd4a
128
Hommersom, C. A.; Matt, B.; van der Ham, A.; Cornelissen, J. J. L. M.; Katsonis, N. Org. Biomol. Chem. 2014, 12, 4065
[ Crossref], [ PubMed], [ CAS], Google Scholar
128
Versatile post-functionalization of the external shell of cowpea chlorotic mottle virus by using click chemistry
Hommersom, C. A.; Matt, B.; van der Ham, A.; Cornelissen, J. J. L. M.; Katsonis, N.
Organic & Biomolecular Chemistry (2014), 12 (24), 4065-4069CODEN: OBCRAK; ISSN:1477-0520. (Royal Society of Chemistry)
We present the modification of the outer protein shell of cowpea chlorotic mottle virus (CCMV) with linear and strained alkyne groups. These functionalized protein capsids constitute valuable platforms for post-functionalization via click chem. After modification, the integrity of the capsid and the reversible disassembly behavior are preserved.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXptVehsbs%253D&md5=7c1180fdfdecafd782d9e1d3ce3ae241
129
Wallace, S.; Chin, J. W. Chem. Sci. 2014, 5, 1742
[ Crossref], [ PubMed], [ CAS], Google Scholar
129
Strain-promoted sydnone bicyclo[6.1.0]nonyne cycloaddition
Wallace, Stephen; Chin, Jason W.
Chemical Science (2014), 5 (5), 1742-1744CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)
The discovery and exploration of bioorthogonal chem. reactions and the biosynthetic incorporation of their components into biomols. for specific labeling is an important challenge. The reaction of a Ph sydnone 1,3-dipole with a bicyclononyne dipolarophile was described. This strain-promoted reaction proceeded without transition metal catalysis in aq. buffer, at physiol. temp., and pressure with a rate comparable to that of other bioorthogonal reactions. We demonstrate the quant. and specific labeling of a genetically encoded bicyclononyne with a sydnone fluorophore conjugate, demonstrating the utility of this approach for bioorthogonal protein labeling.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXlsFOrurw%253D&md5=73aa65d6137cbada75f1e467e1175647
130
Gattner, M. J.; Ehrlich, M.; Vrabel, M. Chem. Commun. 2014, 50, 12568
[ Crossref], [ PubMed], [ CAS], Google Scholar
130
Sulfonyl azide-mediated norbornene aziridination for orthogonal peptide and protein labeling
Gattner, Michael J.; Ehrlich, Michael; Vrabel, Milan
Chemical Communications (Cambridge, United Kingdom) (2014), 50 (83), 12568-12571CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
We describe a new bioconjugation reaction based on the aziridination of norbornenes using electron-deficient sulfonyl azides. The reaction enables to attach various useful tags to peptides and proteins under mild conditions.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsVyhtr%252FJ&md5=0194aaf2cfa74290081d5a1bd97c5fb2
131
(a) Schneider, S.; Gattner, M. J.; Vrabel, M.; Flügel, V.; López-Carrillo, V.; Prill, S.; Carell, T. ChemBioChem 2013, 14, 2114
[ Crossref], [ PubMed], [ CAS], Google Scholar
131a
Structural Insights into Incorporation of Norbornene Amino Acids for Click Modification of Proteins
Schneider, Sabine; Gattner, Michael J.; Vrabel, Milan; Fluegel, Veronika; Lopez-Carrillo, Veronica; Prill, Stefan; Carell, Thomas
ChemBioChem (2013), 14 (16), 2114-2118CODEN: CBCHFX; ISSN:1439-4227. (Wiley-VCH Verlag GmbH & Co. KGaA)
By using a Methanosarcina mazei pyrrolysine synthetase (PylRS) triple mutant (Y306G, Y384F, I405R) the incorporation of two new exo-norbornene-contg. pyrrolysine analogs was achieved. X-ray crystallog. anal. led to the identification of the crucial structural elements involved in substrate recognition by the evolved synthetase.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhsVeisLbN&md5=95fd7ac73dff6fc0137f186cc5f210b4
(b) Han, H.-S.; Devaraj, N. K.; Lee, J.; Hilderbrand, S. A.; Weissleder, R.; Bawendi, M. G. J. Am. Chem. Soc. 2010, 132, 7838
[ ACS Full Text ], [ CAS], Google Scholar
131b
Development of a bioorthogonal and highly efficient conjugation method for quantum dots using tetrazine-norbornene cycloaddn.
Han, Hee-Sun; Devaraj, Neal K.; Lee, Jungmin; Hilderbrand, Scott A.; Weissleder, Ralph; Bawendi, Moungi G.
Journal of the American Chemical Society (2010), 132 (23), 7838-7839CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
We present a bioorthogonal and modular conjugation method for efficient coupling of org. dyes and biomols. to quantum dots (QDs) using a norbornene-tetrazine cycloaddn. The use of noncoordinating functional groups combined with the rapid rate of the cycloaddn. leads to highly efficient conjugation. We have applied this method to the in situ targeting of norbornene-coated QDs to live cancer cells labeled with tetrazine-modified proteins.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXmt12lsLY%253D&md5=e78f454ff98b381b3e68c812074b9939
(c) Kurra, Y.; Odoi, K. A.; Lee, Y.-J.; Yang, Y.; Lu, T.; Wheeler, S. E.; Torres-Kolbus, J.; Deiters, A.; Liu, W. R. Bioconjugate Chem. 2014, 25, 1730
[ ACS Full Text ], [ CAS], Google Scholar
131c
Two Rapid Catalyst-Free Click Reactions for In Vivo Protein Labeling of Genetically Encoded Strained Alkene/Alkyne Functionalities
Kurra, Yadagiri; Odoi, Keturah A.; Lee, Yan-Jiun; Yang, Yanyan; Lu, Tongxiang; Wheeler, Steven E.; Torres-Kolbus, Jessica; Deiters, Alexander; Liu, Wenshe R.
Bioconjugate Chemistry (2014), 25 (9), 1730-1738CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
Detailed kinetic analyses of inverse electron-demand Diels-Alder cycloaddn. and nitrilimine-alkene/alkyne 1,3-dipolar cycloaddn. reactions were conducted and the reactions were applied for rapid protein bioconjugation. When reacted with a tetrazine or a diaryl nitrilimine, strained alkene/alkyne entities including norbornene, trans-cyclooctene, and cyclooctyne displayed rapid kinetics. To apply these "click" reactions for site-specific protein labeling, five tyrosine derivs. that contain a norbornene, trans-cyclooctene, or cyclooctyne entity were genetically encoded into proteins in Escherichia coli using an engineered pyrrolysyl-tRNA synthetase-tRNAPylCUA pair. Proteins bearing these noncanonical amino acids were successively labeled with a fluorescein tetrazine dye and a diaryl nitrilimine both in vitro and in living cells.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsValsbvO&md5=a3871f4ff6141213fe8a43b7d86e7f96
132
(a) Wang, X. S.; Lee, Y.-J.; Liu, W. R. Chem. Commun. 2014, 50, 3176
[ Crossref], [ PubMed], [ CAS], Google Scholar
132a
The nitrilimine-alkene cycloaddition is an ultra rapid click reaction
Wang, Xiaoshan Shayna; Lee, Yan-Jiun; Liu, Wenshe R.
Chemical Communications (Cambridge, United Kingdom) (2014), 50 (24), 3176-3179CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
The transient formation of nitrilimine in aq. conditions is greatly influenced by pH and chloride. In basic conditions (pH 10) with no chloride, a diarylnitrilimine precursor readily ionizes to form diarylnitrilimine that reacts almost instantly with an acrylamide-contg. protein and fluorescently labels it.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXjtFSnsb8%253D&md5=110e7d55cf4cdb059796fad9c551e83d
(b) Lee, Y.-J.; Wu, B.; Raymond, J. E.; Zeng, Y.; Fang, X.; Wooley, K. L.; Liu, W. R. ACS Chem. Biol. 2013, 8, 1664
[ ACS Full Text ], [ CAS], Google Scholar
132b
A Genetically Encoded Acrylamide Functionality
Lee, Yan-Jiun; Wu, Bo; Raymond, Jeffrey E.; Zeng, Yu; Fang, Xinqiang; Wooley, Karen L.; Liu, Wenshe R.
ACS Chemical Biology (2013), 8 (8), 1664-1670CODEN: ACBCCT; ISSN:1554-8929. (American Chemical Society)
Nε-Acryloyl-L-lysine, a noncanonical amino acid with an electron deficient olefin, is genetically encoded in Escherichia coli using a pyrrolysyl-tRNA synthetase mutant in coordination with tRNACUAPyl. The acrylamide moiety is stable in cells, whereas it is active enough to perform a diverse set of unique reactions for protein modifications in vitro. These reactions include 1,4-addn., radical polymn., and 1,3-dipolar cycloaddn. A protein incorporated with Nε-acryloyl-L-lysine is efficiently modified with thiol-contg. nucleophiles at slightly alkali conditions, and the acrylamide moiety also allows rapid radical copolymn. of the same protein into a polyacrylamide hydrogel at physiol. pH. At physiol. conditions, the acrylamide functionality undergoes a fast 1,3-dipolar cycloaddn. reaction with diaryl nitrile imine to show turn-on fluorescence. The authors used this observation to demonstrate site-specific fluorescent labeling of proteins incorporated with Nε-acryloyl-L-lysine both in vitro and in living cells. This crit. development allows easy access to an array of modified proteins for applications where high specificity and reaction efficiency are needed.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXos1ygur8%253D&md5=521788a62a62cbd70ef7d306fe0d9045
(c) Li, F.; Zhang, H.; Sun, Y.; Pan, Y.; Zhou, J.; Wang, J. Angew. Chem., Int. Ed. 2013, 52, 9700
[ Crossref], [ PubMed], [ CAS], Google Scholar
132c
Expanding the genetic code for photoclick chemistry in Escherichia coli, mammalian cells, and Arabidopsis thaliana
Li, Fahui; Zhang, Hua; Sun, Yun; Pan, Yanchao; Zhou, Juanzuo; Wang, Jiangyun
Angewandte Chemie, International Edition (2013), 52 (37), 9700-9704CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
The unnatural amino acid N-ε-acryllysine (AcrK, I) was synthesized and incorporated into proteins in response to an amber stop codon in bacterial cells, mammalian cells, and plants. Genetic selection was used to develop an orthogonal tRNA/aminoacyl-tRNA synthetase pair that would selectively charge I in response to an amber codon. Diaryltetrazole II was chosen for photoclick protein labeling because it is highly reactive for photoclick reactions and sol. in water. I and II were used to label GFP and FtsZ proteins in Escherichia coli. I could be incorporated into EFGP protein in CHO cells. And in Arabidopsis thaliana, I could be incorporated into GFP-mCherry fusion proteins, which could subsequently be labeled with biotin-tetrazole using photoclick chem.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtFCrsrbM&md5=9bdbbb50fed317080bd23d293b9da520
(d) Yu, Z.; Ohulchanskyy, T. Y.; An, P.; Prasad, P. N.; Lin, Q. J. Am. Chem. Soc. 2013, 135, 16766
[ ACS Full Text ], [ CAS], Google Scholar
132d
Fluorogenic, Two-Photon-Triggered Photoclick Chemistry in Live Mammalian Cells
Yu, Zhipeng; Ohulchanskyy, Tymish Y.; An, Peng; Prasad, Paras N.; Lin, Qing
Journal of the American Chemical Society (2013), 135 (45), 16766-16769CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
The tetrazole-based photoclick chem. provides a powerful tool to image proteins in live cells. To extend photoclick chem. to living organisms with improved spatiotemporal control, here the authors report the design of naphthalene-based tetrazoles that can be efficiently activated by two-photon excitation with a 700 nm femtosecond pulsed laser. A water-sol., cell-permeable naphthalene-based tetrazole was identified that reacts with acrylamide with the effective two-photon cross-section for the cycloaddn. reaction detd. to be 3.8 GM. Furthermore, the use of this naphthalene-tetrazole for real-time, spatially controlled imaging of microtubules in live mammalian cells via the fluorogenic, two-photon-triggered photoclick chem. was demonstrated.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhs1yls7zL&md5=c004eb08406925ddb3b7bad043289916
(e) Kaya, E.; Vrabel, M.; Deiml, C.; Prill, S.; Fluxa, V. S.; Carell, T. Angew. Chem., Int. Ed. 2012, 51, 4466
[ Crossref], [ PubMed], [ CAS], Google Scholar
132e
A Genetically Encoded Norbornene Amino Acid for the Mild and Selective Modification of Proteins in a Copper-Free Click Reaction
Kaya, Emine; Vrabel, Milan; Deiml, Christian; Prill, Stefan; Fluxa, Viviana S.; Carell, Thomas
Angewandte Chemie, International Edition (2012), 51 (18), 4466-4469, S4466/1-S4466/30CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
Methods for the site-specific chem. modification of proteins are currently of immense importance for the synthesis of protein-hybrid compds. for pharmaceutical and diagnostic purposes. We have shown here that the generation of nitrile imines from the corresponding hydrazonoyl chlorides by direct HCl elimination under ambient conditions (pH 7.4) followed by reaction with a norbornene-contg. protein gives a fully active, modified protein. The click reaction with the norbornene-contg. protein proceeds with almost quant. yield in just 1 h at room temp. The ability to insert norbornene amino acids into proteins using the pyrrolysine system and the application of a special evolved synthetase now enables the reliable and efficient chem. modification of even sensitive proteins.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XktFyjsr0%253D&md5=fd96adc533070b1aed147a15cb106cba
(f) Lang, K.; Davis, L.; Torres-Kolbus, J.; Chou, C.; Deiters, A.; Chin, J. W. Nat. Chem. 2012, 4, 298
[ Crossref], [ PubMed], [ CAS], Google Scholar
132f
Genetically encoded norbornene directs site-specific cellular protein labelling via a rapid bioorthogonal reaction
Lang, Kathrin; Davis, Lloyd; Torres-Kolbus, Jessica; Chou, Chungjung; Deiters, Alexander; Chin, Jason W.
Nature Chemistry (2012), 4 (4), 298-304CODEN: NCAHBB; ISSN:1755-4330. (Nature Publishing Group)
The site-specific incorporation of bioorthogonal groups via genetic code expansion provides a powerful general strategy for site-specifically labeling proteins with any probe. However, the slow reactivity of the bioorthogonal functional groups that can be encoded genetically limits the utility of this strategy. We demonstrate the genetic encoding of a norbornene amino acid using the pyrrolysyl tRNA synthetase/tRNACUA pair in Escherichia coli and mammalian cells. We developed a series of tetrazine-based probes that exhibit turn-on' fluorescence on their rapid reaction with norbornenes. We demonstrate that the labeling of an encoded norbornene is specific with respect to the entire sol. E. coli proteome and thousands of times faster than established encodable bioorthogonal reactions. We show explicitly the advantages of this approach over state-of-the-art bioorthogonal reactions for protein labeling in vitro and on mammalian cells, and demonstrate the rapid bioorthogonal site-specific labeling of a protein on the mammalian cell surface.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhslGltr4%253D&md5=60615ac32a61d0d970b672b18058296d
(g) Yu, Z.; Pan, Y.; Wang, Z.; Wang, J.; Lin, Q. Angew. Chem., Int. Ed. 2012, 51, 10600
[ Crossref], [ PubMed], [ CAS], Google Scholar
132g
Genetically Encoded Cyclopropene Directs Rapid, Photoclick-Chemistry-Mediated Protein Labeling in Mammalian Cells
Yu, Zhipeng; Pan, Yanchao; Wang, Zhiyong; Wang, Jiangyun; Lin, Qing
Angewandte Chemie, International Edition (2012), 51 (42), 10600-10604CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
The authors report the synthesis of a stable cyclopropene amino acid, the characterization of its reactivity in the photoinduced cycloaddn. reaction with two tetrazoles, its site-specific incorporation into proteins both in E. coli and in mammalian cells, and its use in directing bioorthogonal labeling of proteins both in vitro and in vivo. The authors have demonstrated the genetic incorporation of a cyclopropene-contg. amino acid, CpK, site-specifically into target proteins, and the use of CpK as a bioorthogonal reporter for directing rapid (approx. two minutes) fluorescent labeling of the target protein in mammalian cells.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtlylsbnF&md5=ef89180e457b17a8afce60309811d481
133
Kamber, D. N.; Nazarova, L. A.; Liang, Y.; Lopez, S. A.; Patterson, D. M.; Shih, H.-W.; Houk, K. N.; Prescher, J. A. J. Am. Chem. Soc. 2013, 135, 13680
[ ACS Full Text ], [ CAS], Google Scholar
133
Isomeric Cyclopropenes Exhibit Unique Bioorthogonal Reactivities
Kamber, David N.; Nazarova, Lidia A.; Liang, Yong; Lopez, Steven A.; Patterson, David M.; Shih, Hui-Wen; Houk, K. N.; Prescher, Jennifer A.
Journal of the American Chemical Society (2013), 135 (37), 13680-13683CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
1,3-Disubstituted and 3,3-disubstituted cyclopropenes I (R = H, Me; R1 = Me, H; R2 = Me2CHNH) and II (R = H, Me; R1 = Me, H) were prepd. as biocompatible labeling reagents. I and II (R = H; R1 = Me) underwent chemoselective inverse-electron Diels-Alder cycloaddns. with 1,2,4,5-tetrazines in aq. buffer, while I and II (R = Me; R1 = H) did not undergo Diels-Alder reaction in aq. solvent; I (R = H, Me; R1 = Me, H) underwent photochem. cycloaddn. with a nitrile imine generated in situ from a diaryltetrazole to give either a fluorescent cyclopropapyrazole III or the less fluorescent dihydropyridazine IV. The kinetics of inverse-electron Diels-Alder cycloaddns. of II (R = H, Me; R1 = Me, H) with 1,2,4,5-tetrazines in acetonitrile were detd.; transition state structures and activation barriers for inverse-electron Diels-Alder cycloaddns. were also calcd. Orthogonally reactive scaffolds such as cyclopropenes may provide improved methods for monitoring multicomponent processes in cells and organisms.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtlOksbbN&md5=38bab1a237b03b38c4bc986fe2d99b39
134
Yu, Z.; Lin, Q. J. Am. Chem. Soc. 2014, 136, 4153
[ ACS Full Text ], [ CAS], Google Scholar
134
Design of Spiro[2.3]hex-1-ene, a Genetically Encodable Double-Strained Alkene for Superfast Photoclick Chemistry
Yu, Zhipeng; Lin, Qing
Journal of the American Chemical Society (2014), 136 (11), 4153-4156CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
Reactive yet stable alkene reporters offer a facile route to studying fast biol. processes via the cycloaddn.-based bioorthogonal reactions. Here, the authors report the design and synthesis of a strained spirocyclic alkene, spiro[2.3]hex-1-ene (Sph), for an accelerated photoclick chem., and its site-specific introduction into proteins via amber codon suppression using the wild-type pyrrolysyl-tRNA synthetase/tRNACUA pair. Because of its high ring strain and reduced steric hindrance, Sph exhibited fast reaction kinetics (k2 up to 34,000 M-1s-1) in the photoclick chem. and afforded rapid (<10 s) bioorthogonal protein labeling.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXjsVehs7k%253D&md5=732a856dd87427919e796627badf18ca
135
Darko, A.; Wallace, S.; Dmitrenko, O.; Machovina, M.; Mehl, R.; Chin, J. W.; Fox, J. Chem. Sci. 2014, 5, 3770
[ Crossref], [ PubMed], [ CAS], Google Scholar
135
Conformationally strained trans-cyclooctene with improved stability and excellent reactivity in tetrazine ligation
Darko, Ampofo; Wallace, Stephen; Dmitrenko, Olga; Machovina, Melodie M.; Mehl, Ryan A.; Chin, Jason W.; Fox, Joseph M.
Chemical Science (2014), 5 (10), 3770-3776CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)
Computation has guided the design of conformationally-strained dioxolane-fused trans-cyclooctene (d-TCO) derivs. that display excellent reactivity in the tetrazine ligation. A water sol. deriv. of 3,6-dipyridyl-s-tetrazine reacts with d-TCO with a second order rate k2 366 000 (±15 000) M-1 s-1 at 25 °C in pure water. Furthermore, d-TCO derivs. can be prepd. easily, are accessed through diastereoselective synthesis, and are typically cryst. bench-stable solids that are stable in aq. soln., blood serum, or in the presence of thiols in buffered soln. GFP with a genetically encoded tetrazine-contg. amino acid was site-specifically labeled in vivo by a d-TCO deriv. The fastest bioorthogonal reaction reported to date [k2 3 300 000 (±40 000) M-1 s-1 in H2O at 25 °C] is described herein with a cyclopropane-fused trans-cyclooctene. D-TCO derivs. display rates within an order of magnitude of these fastest trans-cyclooctene reagents, and also display enhanced stability and aq. soly.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtFWhs7%252FP&md5=0c1df5e3978e2b05d7779d828f1928ef
136
(a) Wang, K.; Sachdeva, A.; Cox, D. J.; Wilf, N. W.; Lang, K.; Wallace, S.; Mehl, R. A.; Chin, J. W. Nat. Chem. 2014, 6, 393
[ Crossref], [ PubMed], [ CAS], Google Scholar
136a
Optimized orthogonal translation of unnatural amino acids enables spontaneous protein double-labeling and FRET
Wang, Kaihang; Sachdeva, Amit; Cox, Daniel J.; Wilf, Nabil M.; Lang, Kathrin; Wallace, Stephen; Mehl, Ryan A.; Chin, Jason W.
Nature Chemistry (2014), 6 (5), 393-403CODEN: NCAHBB; ISSN:1755-4330. (Nature Publishing Group)
The ability to introduce different biophys. probes into defined positions in target proteins will provide powerful approaches for interrogating protein structure, function and dynamics. However, methods for site-specifically incorporating multiple distinct unnatural amino acids are hampered by their low efficiency. Here we provide a general soln. to this challenge by developing an optimized orthogonal translation system that uses amber and evolved quadruplet-decoding tRNAs to encode numerous pairs of distinct unnatural amino acids into a single protein expressed in Escherichia coli with a substantial increase in efficiency over previous methods. We also provide a general strategy for labeling pairs of encoded unnatural amino acids with different probes via rapid and spontaneous reactions under physiol. conditions. We demonstrate the utility of our approach by genetically directing the labeling of several pairs of sites in calmodulin with fluorophores and probing protein structure and dynamics by Foerster resonance energy transfer.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXmsVKqsbY%253D&md5=039742f70706d0e67f77d391ed2651e2
(b) Sachdeva, A.; Wang, K.; Elliott, T.; Chin, J. W. J. Am. Chem. Soc. 2014, 136, 7785
[ ACS Full Text ], [ CAS], Google Scholar
136b
Concerted, Rapid, Quantitative, and Site-Specific Dual Labeling of Proteins
Sachdeva, Amit; Wang, Kaihang; Elliott, Thomas; Chin, Jason W.
Journal of the American Chemical Society (2014), 136 (22), 7785-7788CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
Rapid, one-pot, concerted, site-specific labeling of proteins at genetically encoded unnatural amino acids with distinct small mols. at physiol. pH, temp., and pressure is an important challenge. Current approaches require sequential labeling, low pH, and typically days to reach completion, limiting their utility. We report the efficient, genetically encoded incorporation of alkyne- and cyclopropene-contg. amino acids at distinct sites in a protein using an optimized orthogonal translation system in E. coli. and quant., site-specific, one-pot, concerted protein labeling with fluorophores bearing azide and tetrazine groups, resp. Protein double labeling in aq. buffer at physiol. pH, temp., and pressure is quant. in 30 min.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXos1Wlurg%253D&md5=58e3a3c448deb78bf2a2e88ed57a8f9a
137
Floyd, N.; Vijayakrishnan, B.; Koeppe, J. R.; Davis, B. G. Angew. Chem., Int. Ed. 2009, 48, 7798
[ Crossref], [ PubMed], [ CAS], Google Scholar
137
Thiyl Glycosylation of Olefinic Proteins: S-Linked Glycoconjugate Synthesis
Floyd, Nicola; Vijayakrishnan, Balakumar; Koeppe, Julia R.; Davis, Benjamin G.
Angewandte Chemie, International Edition (2009), 48 (42), 7798-7802, S7798/1-S7798/72CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
The authors describe the development of a convergent approach for the synthesis of a novel class of S-linked glycoconjugate proteins through the site-specific ligation of 1-glycosylthiols to proteins. The strategy exploits nonnatural amino acid incorporation for the introduction of L-homoallylglycine (L-Hag) into a protein and free-radical addn. hydrothiolation reactions, under conditions mild enough to retain protein activity throughout. In this way, Hag functions as a new tag combined here with a new modification as part of a general "tag-modify" strategy for synthetic-protein construction. While 1-thioglycoside formation by the free-radical addn. of 1-glycosylthiols to alkenes has been reported for the synthesis of small mols., to date this method has not been applied to the synthesis of S-linked glycoproteins or bioconjugates. The unique reactivity profile of L-Hag, with an olefinic sidechain compared to the natural amino acids characteristically found in proteins, allows for a chemoselective chem. reaction.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXht1ektL%252FN&md5=5de684052119bc60b41972eb8d09467a
138
Li, Q.; Dong, T.; Liu, X.; Lei, X. J. Am. Chem. Soc. 2013, 135, 4996
[ ACS Full Text ], [ CAS], Google Scholar
138
A Bioorthogonal Ligation Enabled by Click Cycloaddition of o-Quinolinone Quinone Methide and Vinyl Thioether
Li, Qiang; Dong, Ting; Liu, Xiaohui; Lei, Xiaoguang
Journal of the American Chemical Society (2013), 135 (13), 4996-4999CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
There is an increasing interest in the use of bioorthogonal ligation to advance biomedical research through selective labeling of biomols. in living systems. Accordingly, discovering new reactions to expand the toolbox of bioorthogonal chem. is of particular interest to chem. biologists. Herein the authors report a new bioorthogonal ligation enabled by click hetero-Diels-Alder (HDA) cycloaddn. of in situ-generated o-quinolinone quinone methides and vinyl thioethers. This reaction is highly selective and proceeds smoothly under aq. conditions. The functionalized vinyl thioethers are small and chem. stable in vivo, making them suitable for use as bioorthogonal chem. reporters that can be effectively coupled to various biomols. The authors used this bioorthogonal ligation for site-specific labeling of proteins as well as imaging of bioactive small mols. inside live cells.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXksFSktrY%253D&md5=b446118ef6fa09c23d0f7070f8327d9c
139
Jouanno, L.-A.; Chevalier, A.; Sekkat, N.; Perzo, N.; Castel, H.; Romieu, A.; Lange, N.; Sabot, C.; Renard, P.-Y. J. Org. Chem. 2014, 79, 10353
[ ACS Full Text ], [ CAS], Google Scholar
139
Kondrat'eva Ligation: Diels-Alder-Based Irreversible Reaction for Bioconjugation
Jouanno, Laurie-Anne; Chevalier, Arnaud; Sekkat, Nawal; Perzo, Nicolas; Castel, Helene; Romieu, Anthony; Lange, Norbert; Sabot, Cyrille; Renard, Pierre-Yves
Journal of Organic Chemistry (2014), 79 (21), 10353-10366CODEN: JOCEAH; ISSN:0022-3263. (American Chemical Society)
Diversification of existing chemoselective ligations is required to efficiently access complex and well-defined biomol. assemblies with unique and valuable properties. The development and bioconjugation applications of a novel Diels-Alder-based irreversible site-specific ligation are reported. The strategy is based on a Kondrat'eva cycloaddn. between bioinert and readily functionalizable 5-alkoxyoxazoles and maleimides that readily react together under mild and easily tunable reaction conditions to afford a fully stable pyridine scaffold. The potential of this novel bioconjugation is demonstrated through the prepn. of fluorescent conjugates of biomols. and a novel Foerster resonance energy transfer (FRET)-based probe suitable for the in vivo detection and imaging of urokinase-like plasminogen activator (uPA), which is a key protease involved in cancer invasion and metastasis.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhslChtr%252FI&md5=ea5065a40a8c8fc9cbcfc9936ef2efa5
140
Engelsma, S. B.; Willems, L. I.; van Paaschen, C. E.; van Kasteren, S. I.; van der Marel, G. A.; Overkleeft, H. S.; Filippov, D. V. Org. Lett. 2014, 16, 2744
[ ACS Full Text ], [ CAS], Google Scholar
140
Acylazetine as a Dienophile in Bioorthogonal Inverse Electron-Demand Diels-Alder Ligation
Engelsma, Sander B.; Willems, Lianne I.; van Paaschen, Claudia E.; van Kasteren, Sander I.; van der Marel, Gijsbert A.; Overkleeft, Herman S.; Filippov, Dmitri V.
Organic Letters (2014), 16 (10), 2744-2747CODEN: ORLEF7; ISSN:1523-7052. (American Chemical Society)
A new bioorthogonal N-acylazetine tag, suitable for tetrazine mediated inverse electron-demand Diels-Alder conjugation, is developed. The tag is small and achiral. The authors demonstrate the usefulness of N-acylazetine-tetrazine based bioorthogonal chem. in two-step activity-based protein profiling. The performance of the new tetrazinophile in the labeling of catalytically active proteasome subunits was comparable to that of the more sterically demanding norbornene tag.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXnsFSlu7c%253D&md5=edc28f2e953876219470cd29a70f6ebf
141
(a) Yang, M.; Li, J.; Chen, P. R. Chem. Soc. Rev. 2014, 43, 6511
[ Crossref], [ PubMed], [ CAS], Google Scholar
141a
Transition metal-mediated bioorthogonal protein chemistry in living cells
Yang, Maiyun; Li, Jie; Chen, Peng R.
Chemical Society Reviews (2014), 43 (18), 6511-6526CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)
A review. Considerable attention has been focused on improving the biocompatibility of Cu(I)-catalyzed azide-alkyne cycloaddn. (CuAAC), a hallmark of bioorthogonal reaction, in living cells. Besides creating copper-free versions of click chem. such as strain promoted azide-alkyne cycloaddn. (SPAAC), a central effort has also been made to develop various Cu(I) ligands that can prevent the cytotoxicity of Cu(I) ions while accelerating the CuAAC reaction. Meanwhile, addnl. transition metals such as palladium have been explored as alternative sources to promote a bioorthogonal conjugation reaction on cell surface, as well as within an intracellular environment. Furthermore, transition metal mediated chem. conversions beyond conjugation have also been utilized to manipulate protein activity within living systems. We highlight these emerging examples that significantly enriched our protein chem. toolkit, which will likely expand our view on the definition and applications of bioorthogonal chem.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtlOjt7vE&md5=bdb2ff120d8e0c77dfb30fe762d6c1f0
(b) Chankeshwara, S. V.; Indrigo, E.; Bradley, M. Curr. Opin. Chem. Biol. 2014, 21, 128
[ Crossref], [ PubMed], [ CAS], Google Scholar
141b
Palladium-mediated chemistry in living cells
Chankeshwara, Sunay V.; Indrigo, Eugenio; Bradley, Mark
Current Opinion in Chemical Biology (2014), 21 (), 128-135CODEN: COCBF4; ISSN:1367-5931. (Elsevier B.V.)
A review. Bioorthogonal metal-catalyzed chem. is the application of biocompatible transition metals to catalyze conventional synthetic org. chem. reactions within a biol. environment. Over the past decade, metals which were previously restricted to conventional org. synthesis have begun to be used in an increasing no. of biol. settings. This has been dominated by copper mediated catalysis of the azide-alkyne Huisgen cycloaddn. (1,3-dipolar addn.) chem. but other, less toxic, metals such as palladium are now beginning to establish themselves in the chem. biol./chem. medicine arenas. The potential of palladium mediated chem. in living systems now ranges from protein modifications to in cellulo synthesis or activation of drugs and suggests that palladium chem. has the potential to become a powerful tool. In this review we highlight recent advances in Pd-mediated reactions in living systems.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtleis7vJ&md5=835b177be06970103017428687f584e7
142
(a) Sasmal, P. K.; Streu, C. N.; Meggers, E. Chem. Commun. 2013, 49, 1581
[ Crossref], [ PubMed], [ CAS], Google Scholar
142a
Metal complex catalysis in living biological systems
Sasmal, Pijus K.; Streu, Craig N.; Meggers, Eric
Chemical Communications (Cambridge, United Kingdom) (2013), 49 (16), 1581-1587CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
A review. This feature article discusses synthetic metal complexes that are capable of catalyzing chem. transformations in living organisms. Photodynamic therapy exemplifies what is probably the most established artificial catalytic process exploited in medicine, namely the photosensitized catalytic generation of cell-damaging singlet oxygen. Different redox catalysts have been designed over the last two decades to target a variety of redox alterations in cancer and other diseases. For example, pentaazamacrocyclic manganese(ii) complexes catalyze the dismutation of superoxide to O2 and H2O2in vivo and thus reduce oxidative stress in analogy to the native enzyme superoxide dismutase. Recently, piano-stool ruthenium and iridium complexes were reported to influence cellular redox homeostasis indirectly by catalytic glutathione oxidn. and catalytic transfer hydrogenation using the coenzyme NADH, resp. Over the last few years, significant progress was made towards the application of non-biol. reactions in living systems, ranging from the organoruthenium-catalyzed cleavage of alkylcarbamates and a gold-catalyzed intramol. hydroarylation to palladium-catalyzed Suzuki-Miyaura and Sonogashira cross-couplings within the cytoplasm or on the surface of living cells. The design of bioorthogonal catalyst/substrate pairs, which can passively diffuse into cells, combines the advantages of small mols. with catalysis and promises to provide exciting new tools for future chem. biol. studies.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhsFGqs7k%253D&md5=8fda2885942e7d87ff196d4f5f64c491
(b) Antos, J. M.; Francis, M. B. Curr. Opin. Chem. Biol. 2006, 10, 253
[ Crossref], [ PubMed], [ CAS], Google Scholar
142b
Transition metal catalyzed methods for site-selective protein modification
Antos, John M.; Francis, Matthew B.
Current Opinion in Chemical Biology (2006), 10 (3), 253-262CODEN: COCBF4; ISSN:1367-5931. (Elsevier B.V.)
A review. The broad utility of protein bioconjugates has created a need for new and diverse strategies for site-selective protein modification. In particular, chem. reactions that target alternative amino acid side chains or unnatural functional groups are emerging as a valuable complement to more commonly used lysine- and cysteine-based strategies. Considering their widespread use in org. synthesis, reactions catalyzed by transition metals could provide a particularly powerful set of transformations for the continued expansion of the bioconjugation toolkit. Recent efforts to apply transition metal catalysis to protein modification have resulted in new methods for protein crosslinking, tryptophan modification, tyrosine modification, reductive amination of protein amines, and unnatural amino acid labeling. These strategies have substantially expanded the synthetic flexibility of protein modification, and thus the range of applications for which bioconjugates can be used in chem. biol. and materials science.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28XltlKkt7c%253D&md5=6626f916736e808e8502459f30da9dd5
143
McFarland, J. M.; Francis, M. B. J. Am. Chem. Soc. 2005, 127, 13490
[ ACS Full Text ], [ CAS], Google Scholar
143
Reductive Alkylation of Proteins Using Iridium Catalyzed Transfer Hydrogenation
McFarland, Jesse M.; Francis, Matthew B.
Journal of the American Chemical Society (2005), 127 (39), 13490-13491CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
An efficient transition metal catalyzed procedure for the reductive alkylation of proteins has been developed. Imines formed from the condensation of aldehydes (1 mM) with lysine residues and the N-terminus can be reduced efficiently by a [Cp*Ir(4,4'-dimethoxy-2,2'-bipyridine)(H2O)]SO4 catalyst in the presence of formate ions. The reaction proceeds readily at pH 7.4 in aq. phosphate buffer at temps. ranging from 22 to 37°, and reaches high levels of conversion for a no. of arom. aldehydes. UV expts. have confirmed that the catalyst does not bind to protein substrates. The utility of the reaction has been demonstrated through an efficient two-step procedure for the attachment of unfunctionalized poly(ethylene glycol) to protein targets.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXpslequrk%253D&md5=a1e9f5e3ce701be690116ba1ee113870
144
Tilley, S. D.; Francis, M. B. J. Am. Chem. Soc. 2006, 128, 1080
[ ACS Full Text ], [ CAS], Google Scholar
144
Tyrosine-Selective Protein Alkylation Using π-Allylpalladium Complexes
Tilley, S. David; Francis, Matthew B.
Journal of the American Chemical Society (2006), 128 (4), 1080-1081CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
A new protein modification reaction has been developed based on a palladium-catalyzed allylic alkylation of tyrosine residues. This technique employs electrophilic π-allyl intermediates derived from allylic acetate and carbamate precursors and can be used to modify proteins in aq. soln. at room temp. To facilitate the detection of modified proteins using SDS-PAGE anal., a fluorescent allyl acetate was synthesized and coupled to chymotrypsinogen A and bacteriophage MS2. The tyrosine selectivity of the reaction was confirmed through trypsin digest anal. The utility of the reaction was demonstrated by using taurine-derived carbamates as water solubilizing groups that are cleaved upon protein functionalization. This soly. switching technique was used to install hydrophobic farnesyl and C17 chains on chymotrypsinogen A in water using little or no cosolvent. Following this, the C17 alkylated proteins were found to assoc. with lipid vesicles. In addn. to providing a new protein modification strategy targeting an underutilized amino acid side chain, this method provides convenient access to synthetic lipoproteins.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28XitVymsw%253D%253D&md5=8881b14279e96462847e868e6ede7c7e
145
Chen, S.; Li, X.; Ma, H. ChemBioChem 2009, 10, 1200
[ Crossref], [ PubMed], [ CAS], Google Scholar
145
New Approach for Local Structure Analysis of the Tyrosine Domain in Proteins by Using a Site-Specific and Polarity-Sensitive Fluorescent Probe
Chen, Suming; Li, Xiaohua; Ma, Huimin
ChemBioChem (2009), 10 (7), 1200-1207CODEN: CBCHFX; ISSN:1439-4227. (Wiley-VCH Verlag GmbH & Co. KGaA)
Design and synthesis of a novel long-wavelength polarity-sensitive fluorescence probe, 6-[9-(diethylamino)-5-oxo-5 H-benzo[α]phenoxazin-2-yloxy]hex-2-enyl acetate, for the selective modification of tyrosine residues with the goal of providing local information on tyrosine domains in proteins, is reported. This probe comprises a polarity-sensitive Nile red fluorophore and an active π-allyl group that can form π-allylpalladium complexes and react selectively with tyrosine residues. Probe has the following features: 1) it has a long-wavelength emission of >550 nm, thanks to which interference from short-wavelength fluorescence from common biol. matrixes can be avoided; 2) the max. emission wavelength is sensitive only to polarity and not to pH or temp.; this allows the accurate detn. of local polarity; and 3) it is a neutral, uncharged mol., and does not disturb the overall charge of the labeled protein. With this probe the polarity and conformation changes of the Tyr108 domain in native and in acid- and heat-denatured bovine Cu/Zn superoxide dismutase were detected for the first time. It was found that the polarity of the Tyr108 domain hardly alters on acid denaturation between pH 4 and 9. However, heat denaturation caused the Tyr108 domain to be more hydrophobic, and was accompanied by an irreversible aggregation of the protein. In addn., the probe-binding expts. revealed that the surface of the protein becomes more hydrophobic after thermal denaturation; this can be ascribed to the formation of the more hydrophobic aggregates. This strategy might provide a general approach for studying the local environment changes of tyrosine domains in proteins under acid or heat denaturation conditions.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXmtVOntr4%253D&md5=e8597b98147adefc98ad29dc8a1a1cab
146
Cserép, G. B.; Herner, A.; Wolfbeis, O. S.; Kele, P. Bioorg. Med. Chem. Lett. 2013, 23, 5776
[ Crossref], [ PubMed], [ CAS], Google Scholar
146
Tyrosine specific sequential labeling of proteins
Cserep, Gergely B.; Herner, Andras; Wolfbeis, Otto S.; Kele, Peter
Bioorganic & Medicinal Chemistry Letters (2013), 23 (21), 5776-5778CODEN: BMCLE8; ISSN:0960-894X. (Elsevier B.V.)
We report (a) on the synthesis of a long-wavelength fluorescent coumarin contg. an allyloxy acetate moiety, (b) the synthesis of two linkers contg. an allyloxy acetate and an alkyne or azide function, resp., and (c) the selective modification human serum albumin by a sequential method involving Pd(II) catalyzed modification of the phenolic side chain of tyrosine residues with an alkyne bearing linker and a subsequent azide-alkyne click reaction with an azide functionalized long-wavelength emitting coumarin dye. The method is likely to be applicable to various kinds of azido-modified fluorophores, and the Pd(II)-catalyzed modification of the tyrosines may also be used to introduce other kinds of tags. With these reagents, tyrosine specific modulation of proteins and peptides becomes possible either directly or in a sequential manner.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhsFaksLnL&md5=c6687310f4b084406df5153851c8db70
147
(a) Obermeyer, A. C.; Jarman, J. B.; Netirojjanakul, C.; El Muslemany, K.; Francis, M. B. Angew. Chem., Int. Ed. 2014, 53, 1057
[ Crossref], [ PubMed], [ CAS], Google Scholar
147a
Mild Bioconjugation Through the Oxidative Coupling of ortho-Aminophenols and Anilines with Ferricyanide
Obermeyer, Allie C.; Jarman, John B.; Netirojjanakul, Chawita; El Muslemany, Kareem; Francis, Matthew B.
Angewandte Chemie, International Edition (2014), 53 (4), 1057-1061CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
Using a small-mol.-based screen, ferricyanide was identified as a mild and efficient oxidant for the coupling of anilines and o-aminophenols on protein substrates. This reaction is compatible with thiols and 1,2-diols, allowing its use in the creation of complex bioconjugates for use in biotechnol. and materials applications.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhvVykt7zE&md5=181fc5a090d96ebce0f4e7cc7f2b414f
(b) Ji, A.; Ren, W.; Ai, H.-W. Chem. Commun. 2014, 50, 7469
[ Crossref], [ PubMed], [ CAS], Google Scholar
147b
A highly efficient oxidative condensation reaction for selective protein conjugation
Ji, Ao; Ren, Wei; Ai, Hui-wang
Chemical Communications (Cambridge, United Kingdom) (2014), 50 (56), 7469-7472CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
We hereby report a mild and efficient coupling reaction between alkyl aldehydes and aryl diamines. In the presence of a Cu2+ or a Zn2+ ion, oxygen (O2) in air is able to promote the oxidative condensation of the two readily preparable functional groups, forming stable benzimidazole linkages in neutral aq. soln. at room temp. (RT). We demonstrated that the reaction could be utilized to label a T4 lysozyme protein contg. a chem. installed aryl diamine group with a fluorescent aldehyde dye mol. at 37 °C.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtVagur3N&md5=f5905e813ad3d2c97c1c8f7f2fcdaaea
(c) Obermeyer, A. C.; Jarman, J. B.; Francis, M. B. J. Am. Chem. Soc. 2014, 136, 9572
[ ACS Full Text ], [ CAS], Google Scholar
147c
N-Terminal Modification of Proteins with o-Aminophenols
Obermeyer, Allie C.; Jarman, John B.; Francis, Matthew B.
Journal of the American Chemical Society (2014), 136 (27), 9572-9579CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
The synthetic modification of proteins plays an important role in chem. biol. and biomaterials science. These fields provide a const. need for chem. tools that can introduce new functionality in specific locations on protein surfaces. In this work, an oxidative strategy is demonstrated for the efficient modification of N-terminal residues on peptides and N-terminal proline residues on proteins. The strategy uses o-aminophenols or o-catechols that are oxidized to active coupling species in situ using potassium ferricyanide. Peptide screening results have revealed that many N-terminal amino acids can participate in this reaction, and that proline residues are particularly reactive. When applied to protein substrates, the reaction shows a stronger requirement for the proline group. Key advantages of the reaction include its fast second-order kinetics and ability to achieve site-selective modification in a single step using low concns. of reagent. Although free cysteines are also modified by the coupling reaction, they can be protected through disulfide formation and then liberated after N-terminal coupling is complete. This allows access to doubly functionalized bioconjugates that can be difficult to access using other methods.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtVGlu77L&md5=ab16257753b27283d65e3d787b0bff7f
(d) Seim, K. L.; Obermeyer, A. C.; Francis, M. B. J. Am. Chem. Soc. 2011, 133, 16970
[ ACS Full Text ], [ CAS], Google Scholar
147d
Oxidative Modification of Native Protein Residues Using Cerium(IV) Ammonium Nitrate
Seim, Kristen L.; Obermeyer, Allie C.; Francis, Matthew B.
Journal of the American Chemical Society (2011), 133 (42), 16970-16976CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
A new protein modification strategy has been developed that is based on an oxidative coupling reaction that targets electron-rich amino acids. This strategy relies on cerium(IV) ammonium nitrate (CAN) as an oxidn. reagent and results in the coupling of tyrosine and tryptophan residues to phenylene diamine and anisidine derivs. The methodol. was first identified and characterized on peptides and small mols., and was subsequently adapted for protein modification by detg. appropriate buffer conditions. Using the optimized procedure, native and introduced solvent-accessible residues on proteins were selectively modified with polyethylene glycol (PEG) and small peptides. This unprecedented bioconjugation strategy targets these under-utilized amino acids with excellent chemoselectivity and affords good-to-high yields using low concns. of the oxidant and coupling partners, short reaction times, and mild conditions.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXht1GitLrO&md5=d32af6997266005a5bf1856e09eb8c0c
148
Antos, J. M.; Francis, M. B. J. Am. Chem. Soc. 2004, 126, 10256
[ ACS Full Text ], [ CAS], Google Scholar
148
Selective tryptophan modification with rhodium carbenoids in aqueous solution
Antos, John M.; Francis, Matthew B.
Journal of the American Chemical Society (2004), 126 (33), 10256-10257CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
A new transition metal-based reaction has been developed for the selective modification of tryptophan residues on protein substrates. After activation of vinyl-substituted diazo compds. by Rh2(OAc)4, the resulting metallocarbenoid intermediates were found to modify indoles in aq. media despite competing reactions with water. Both N- and 2-substituted indole products were obsd. in the reaction. Following initial small-mol. studies, the reaction was performed on two protein substrates. Both myoglobin and subtilisin Carlsberg were modified readily in aq. soln., and the tryptophan selectivity of the reactions was confirmed through MS analyses of trypsin digest fragments. It was also demonstrated that myoglobin concns. as low as 10 μM still led to appreciable levels of modification. Reconstitution expts. confirmed that myoglobin retained its ability to bind heme following modification.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXmtVOjtrc%253D&md5=e4a855e9cdb8e6c6b44b321dd898106d
149
Antos, J. M.; McFarland, J. M.; Iavarone, A. T.; Francis, M. B. J. Am. Chem. Soc. 2009, 131, 6301
[ ACS Full Text ], [ CAS], Google Scholar
149
Chemoselective Tryptophan Labeling with Rhodium Carbenoids at Mild pH
Antos, John M.; McFarland, Jesse M.; Iavarone, Anthony T.; Francis, Matthew B.
Journal of the American Chemical Society (2009), 131 (17), 6301-6308CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
Significant improvements have been made to a previously reported tryptophan modification method using rhodium carbenoids in aq. soln., allowing the reaction to proceed at pH 6-7. This technique is based on the discovery that N-(tert-butyl)hydroxylamine promotes indole modification with rhodium carbenoids over a broad pH range (2-7). This methodol. was demonstrated on peptide and protein substrates, generally yielding 40-60% conversion with excellent tryptophan chemoselectivity. The solvent accessibility of the indole side chains was a key factor in successful carbenoid addn., as demonstrated by conducting the reaction at temps. high enough to cause thermal denaturation of the protein substrate. Progress toward the expression of proteins bearing solvent accessible tryptophan residues as reactive handles for modification with rhodium carbenoids is also reported.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXksV2isrw%253D&md5=5c14c7fa813430af98264d990d2103ba
150
Kundu, R.; Ball, Z. T. Chem. Commun. 2013, 49, 4166
[ Crossref], [ PubMed], [ CAS], Google Scholar
150
Rhodium-catalyzed cysteine modification with diazo reagents
Kundu, Rituparna; Ball, Zachary T.
Chemical Communications (Cambridge, United Kingdom) (2013), 49 (39), 4166-4168CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
A simple rhodium(II) complex catalyzes cysteine modification with diazo reagents. The reaction is marked by clean cysteine selectivity and mild reaction conditions. The resulting linkage is significantly more stable in human plasma serum, when compared to common maleimide reagents.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXmt1Cju78%253D&md5=9575bb0fbdd0b32c5af16b6d8182f6b7
151
Gillingham, D.; Fei, N. Chem. Soc. Rev. 2013, 42, 4918
[ Crossref], [ PubMed], [ CAS], Google Scholar
151
Catalytic X-H insertion reactions based on carbenoids
Gillingham, Dennis; Fei, Na
Chemical Society Reviews (2013), 42 (12), 4918-4931CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)
A review. Catalyzed X-H insertion reactions into diazo compds. (X is any heteroatom) are a powerful yet underused class of transformations. The following review will explore the historical development of X-H insertion and give an up-to-date account of the metal catalysts most often employed, including an assessment of their strengths and weaknesses. Despite decades of development, recent work on enantioselective variants, as well as applying catalytic X-H insertion towards problems in chem. biol. indicate that this field has ample room for innovation.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXot1ersLk%253D&md5=7525f0a6d7724440ce89ce94f3f6e00c
152
On-Yee Chan, A.; Lui-Lui Tsai, J.; Kar-Yan Lo, V.; Li, G.-L.; Wong, M.-K.; Che, C.-M. Chem. Commun. 2013, 49, 1428
[ Crossref], [ PubMed], Google Scholar
There is no corresponding record for this reference.
153
Liu, C. C.; Schultz, P. G. Annu. Rev. Biochem. 2010, 79, 413
[ Crossref], [ PubMed], [ CAS], Google Scholar
153
Adding new chemistries to the genetic code
Liu, Chang C.; Schultz, Peter G.
Annual Review of Biochemistry (2010), 79 (), 413-444CODEN: ARBOAW; ISSN:0066-4154. (Annual Reviews Inc.)
A review. The development of new orthogonal aminoacyl-tRNA synthetase/tRNA pairs has led to the addn. of approx. 70 unnatural amino acids (UAAs) to the genetic codes of Escherichia coli, yeast, and mammalian cells. These UAAs represent a wide range of structures and functions not found in the canonical 20 amino acids and thus provide new opportunities to generate proteins with enhanced or novel properties and probes of protein structure and function.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXpslShtrg%253D&md5=ce1f7de331d6a3b337678e7422c78239
154
(a) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B. Angew. Chem., Int. Ed. 2002, 41, 2596
[ Crossref], [ PubMed], [ CAS], Google Scholar
154a
A stepwise Huisgen cycloaddition process: copper(I)-catalyzed regioselective "ligation" of azides and terminal alkynes
Rostovtsev, Vsevolod V.; Green, Luke G.; Fokin, Valery V.; Sharpless, K. Barry
Angewandte Chemie, International Edition (2002), 41 (14), 2596-2599CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH)
1,4-Disubstituted 1,2,3-triazoles I (R1 = PhCH2, PhCH2OCH2, 1-adamantyl, etc.; R2 = HO2C, Ph, PhOCH2, Et2NCH2, etc.) were readily and cleanly prepd. via highly efficient and regioselective copper(I)-catalyzed cycloaddn. of azides R1N3 with terminal alkynes R2C≡CH in 82-93% yields.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD38Xls1Ohsr4%253D&md5=4603664be6639353b5e70f19b9f8d59f
(b) Tornoe, C. W.; Christensen, C.; Meldal, M. J. Org. Chem. 2002, 67, 3057
[ ACS Full Text ], [ CAS], Google Scholar
154b
Peptidotriazoles on Solid Phase: [1,2,3]-Triazoles by Regiospecific Copper(I)-Catalyzed 1,3-Dipolar Cycloadditions of Terminal Alkynes to Azides
Tornoe, Christian W.; Christensen, Caspar; Meldal, Morten
Journal of Organic Chemistry (2002), 67 (9), 3057-3064CODEN: JOCEAH; ISSN:0022-3263. (American Chemical Society)
The cycloaddn. of azides to alkynes is one of the most important synthetic routes to 1H-[1,2,3]-triazoles. This work reports a novel regiospecific copper(I)-catalyzed 1,3-dipolar cycloaddn. of terminal alkynes to azides on solid-phase. Primary, secondary, and tertiary alkyl azides, aryl azides, and an azido sugar were used successfully in the copper(I)-catalyzed cycloaddn. producing diversely 1,4-substituted [1,2,3]-triazoles in peptide backbones or side chains. The reaction conditions were fully compatible with solid-phase peptide synthesis on polar supports. The copper(I) catalysis is mild and efficient (>95% conversion and purity in most cases) and furthermore, the x-ray structure of 2-azido-2-methylpropanoic acid has been solved, to yield structural information on the 1,3-dipoles entering the reaction. Novel Fmoc-protected amino azides were prepd. from Fmoc-amino alcs. by Mitsunobu reaction.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD38XisVeks7w%253D&md5=6b3b805572783873952871f1b69f46dd
155
van Kasteren, S. I.; Kramer, H. B.; Jensen, H. H.; Campbell, S. J.; Kirkpatrick, J.; Oldham, N. J.; Anthony, D. C.; Davis, B. G. Nature 2007, 446, 1105
[ Crossref], [ PubMed], [ CAS], Google Scholar
155
Expanding the diversity of chemical protein modification allows post-translational mimicry
van Kasteren, Sander I.; Kramer, Holger B.; Jensen, Henrik H.; Campbell, Sandra J.; Kirkpatrick, Joanna; Oldham, Neil J.; Anthony, Daniel C.; Davis, Benjamin G.
Nature (London, United Kingdom) (2007), 446 (7139), 1105-1109CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)
One of the most important current scientific paradoxes is the economy with which nature uses genes. In all higher animals studied, many fewer genes have been found than would have previously expected. The functional outputs of the eventual products of genes seem to be far more complex than the more restricted blueprint. In higher organisms, the functions of many proteins are modulated by post-translational modifications (PTMs). These alterations of amino-acid side chains lead to higher structural and functional protein diversity and are, therefore, a leading contender for an explanation for this seeming incongruity. Natural protein prodn. methods typically produce PTM mixts. within which function is difficult to dissect or control. Until now it has not been possible to access pure mimics of complex PTMs. Here the authors report a chem. tagging approach that enables the attachment of multiple modifications to bacterially expressed (bare) protein scaffolds: this approach allows reconstitution of functionally effective mimics of higher organism PTMs. By attaching appropriate modifications at suitable distances in the widely-used LacZ reporter enzyme scaffold, the authors created protein probes that included sensitive systems for detection of mammalian brain inflammation and disease. Through target synthesis of the desired modification, chem. provides a structural precision and an ability to retool with a chosen PTM in a manner not available to other approaches. In this way, combining chem. control of PTM with readily available protein scaffolds provides a systematic platform for creating probes of protein-PTM interactions. The authors therefore anticipate that this ability to build model systems will allow some of this gene product complexity to be dissected, with the aim of eventually being able to completely duplicate the patterns of a particular protein's PTMs from an in vivo assay into an in vitro system.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXksFeku7k%253D&md5=2cfb6409a93effd9f5a6fac9d8e5393e
156
Raliski, B. K.; Howard, C. A.; Young, D. D. Bioconjugate Chem. 2014, 25, 1916
[ ACS Full Text ], [ CAS], Google Scholar
156
Site-Specific Protein Immobilization Using Unnatural Amino Acids
Raliski, Benjamin K.; Howard, Christina A.; Young, Douglas D.
Bioconjugate Chemistry (2014), 25 (11), 1916-1920CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
Protein immobilization confers the advantages of biol. systems to a more chem. setting and has applications in catalysis, sensors, and materials development. While numerous immobilization techniques exist, it is optimal to develop a well-defined and chem. stable methodol. to allow for full protein function. This paper describes the utilization of unnatural amino acid technologies to introduce bioorthogonal handles in a site-specific fashion for protein immobilization. To develop this approach a range of solid-supports, org. linkers, and protein immobilization sites have been investigated using a GFP reporter system. Overall, a sepharose resin derivatized with propargyl alc. has afforded the highest yields of immobilized protein. Moreover, an unnatural amino acid residue protein context has been demonstrated, signifying a necessity to consider the protein site of immobilization. Finally, a resin-conferred stabilization was demonstrated in several org. solvents.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsl2ht73N&md5=a9bd97dac75c7d2eca300a07e6e7ed07
157
Boutureira, O.; D’Hooge, F.; Fernández-González, M.; Bernardes, G. J. L.; Sánchez-Navarro, M.; Koeppe, J. R.; Davis, B. G. Chem. Commun. 2010, 46, 8142
[ Crossref], [ PubMed], [ CAS], Google Scholar
157
Fluoroglycoproteins: ready chemical site-selective incorporation of fluorosugars into proteins
Boutureira, Omar; D'Hooge, Francois; Fernandez-Gonzalez, Marta; Bernardes, Goncalo J. L.; Sanchez-Navarro, Macarena; Koeppe, Julia R.; Davis, Benjamin G.
Chemical Communications (Cambridge, United Kingdom) (2010), 46 (43), 8142-8144CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
A tag-and-modify strategy allows the practical synthesis of homogeneous fluorinated glyco-amino acids, peptides and proteins carrying a fluorine label in the sugar and allows access to first examples of directly radiolabeled ([18F]-glyco)proteins.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhtlentbvM&md5=e0047684173aba2d6adc8f4e6aea9606
158
Diaz Velazquez, H.; Ruiz Garcia, Y.; Vandichel, M.; Madder, A.; Verpoort, F. Org. Biomol. Chem. 2014, 12, 9350
[ Crossref], [ PubMed], [ CAS], Google Scholar
158
Water-soluble NHC-Cu catalysts: applications in click chemistry, bioconjugation and mechanistic analysis
Diaz Velazquez, Heriberto; Ruiz Garcia, Yara; Vandichel, Matthias; Madder, Annemieke; Verpoort, Francis
Organic & Biomolecular Chemistry (2014), 12 (46), 9350-9356CODEN: OBCRAK; ISSN:1477-0520. (Royal Society of Chemistry)
Water-sol. copper(I) 2-imidazolidinylidene NHC complexes functionalized with sulfonate groups, [[1-Mes-3-[(CH2)nSO3K]C3H4N2]2Cu][PF6] (5, 6, n = 3, 4) and their 2-imidazolylidene counterparts [[1-Mes-3-[(CH2)nSO3K]C3H2N2]2Cu][PF6] (7, 8, n = 3, 4) were prepd. and evaluated for their catalytic activity in azide-alkyne click 1,3-dipolar cycloaddn., Staudinger amination and bioconjugation reactions. Copper(I)-catalyzed 1,3-dipolar cycloaddn. of azides and terminal alkynes (CuAAC), better known as "click" reaction, has triggered the use of 1,2,3-triazoles in bioconjugation, drug discovery, materials science and combinatorial chem. Here we report a new series of water-sol. catalysts based on N-heterocyclic carbene (NHC)-Cu complexes which are addnl. functionalized with a sulfonate group. The complexes show superior activity towards CuAAC reactions and display a high versatility, enabling the prodn. of triazoles with different substitution patterns. Addnl., successful application of these complexes in bioconjugation using unprotected peptides acting as DNA binding domains was achieved for the first time. Mechanistic insight into the reaction mechanism is obtained by means of state-of-the-art first principles calcns.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsVyrsLnM&md5=336505e23f6b177e85a0cdd9fce1b78e
159
(a) Besanceney-Webler, C.; Jiang, H.; Zheng, T.; Feng, L.; Soriano del Amo, D.; Wang, W.; Klivansky, L. M.; Marlow, F. L.; Liu, Y.; Wu, P. Angew. Chem., Int. Ed. 2011, 50, 8051
[ Crossref], [ PubMed], [ CAS], Google Scholar
159a
Increasing the Efficacy of Bioorthogonal Click Reactions for Bioconjugation: A Comparative Study
Besanceney-Webler, Christen; Jiang, Hao; Zheng, Tianqing; Feng, Lei; Soriano del Amo, David; Wang, Wei; Klivansky, Liana M.; Marlow, Florence L.; Liu, Yi; Wu, Peng
Angewandte Chemie, International Edition (2011), 50 (35), 8051-8056, S8051/1-S8051/19CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
The parallel comparison of the bioorthogonal click reactions, namely the strain-promoted copper-free cycloaddn. and the ligand-accelerated CuAAC, verifies the great potential of the latter as a highly effective ligation tool for broad biol. applications. With the discovery of a new accelerating ligand for CuAAC, not only are kinetics that are faster than those of the known catalysts achieved, but more importantly, it allows for effective bioconjugation with suppressed cell cytotoxicity by further lowering CuI loading in the catalyst formulation. Although CuAAC requires multiple reagents to promote the reaction, which is more complicated compared to the copper-free click chem. where only one single reagent is used, the reaction conditions optimized here are the most effective in four biol. settings, i.e., labeling of recombinant glycoproteins, glycoproteins in crude cell lysates and on live cell surfaces, and in the enveloping layer of zebrafish embryos. An addnl. advantage of the bio-benign CuAAC is that it liberates the bioconjugation from the limitation where ligations could only be accomplished with azide-tagged biomols. Terminal alkyne residues can now also be incorporated into biomols. and detected in vivo. Overall, the reported ligand-accelerated CuAAC represents a powerful and highly adaptive bioconjugation tool for biologists, which holds great promise for further improvement with the discovery of more versatile catalyst systems.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXovVOhtbY%253D&md5=3d05dd94eceb1c53bd26c2bff1bffe0e
(b) Kennedy, D. C.; McKay, C. S.; Legault, M. C. B.; Danielson, D. C.; Blake, J. A.; Pegoraro, A. F.; Stolow, A.; Mester, Z.; Pezacki, J. P. J. Am. Chem. Soc. 2011, 133, 17993
[ ACS Full Text ], [ CAS], Google Scholar
159b
Cellular Consequences of Copper Complexes Used To Catalyze Bioorthogonal Click Reactions
Kennedy, David C.; McKay, Craig S.; Legault, Marc C. B.; Danielson, Dana C.; Blake, Jessie A.; Pegoraro, Adrian F.; Stolow, Albert; Mester, Zoltan; Pezacki, John Paul
Journal of the American Chemical Society (2011), 133 (44), 17993-18001CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
Copper toxicity is a crit. issue in the development of copper-based catalysts for copper(I)-catalyzed azide-alkyne cycloaddn. (CuAAC) reactions for applications in living systems. The effects and related toxicity of copper on mammalian cells are dependent on the ligand environment. Copper complexes can be highly toxic, can induce changes in cellular metab., and can be rapidly taken up by cells, all of which can affect their ability to function as catalysts for CuAAC in living systems. Herein, the authors have evaluated the effects of a no. of copper complexes that are typically used to catalyze CuAAC reactions on four human cell lines by measuring mitochondrial activity based on the metab. of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) to study toxicity, inductively coupled plasma mass spectrometry to study cellular uptake, and coherent anti-Stokes Raman scattering (CARS) microscopy to study effects on lipid metab. The authors find that ligand environment around copper influences all three parameters. Interestingly, for the Cu(II)-bis-L-histidine complex (Cu(his)2), cellular uptake and metabolic changes are obsd. with no toxicity after 72 h at micromolar concns. Furthermore, the authors show that under conditions where other copper complexes kill human hepatoma cells, Cu(I)-L-histidine is an effective catalyst for CuAAC labeling of live cells following metabolic incorporation of an alkyne-labeled sugar (Ac4ManNAl) into glycosylated proteins expressed on the cell surface. This result suggests that Cu(his)2 or derivs. thereof have potential for in vivo applications where toxicity as well as catalytic activity are crit. factors for successful bioconjugation reactions.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhtlCiurnJ&md5=ef9ed794ec654b5cd8aeb9220b14ba78
(c) Hong, V.; Presolski, S. I.; Ma, C.; Finn, M. G. Angew. Chem., Int. Ed. 2009, 48, 9879
[ Crossref], [ PubMed], [ CAS], Google Scholar
159c
Analysis and Optimization of Copper-Catalyzed Azide-Alkyne Cycloaddition for Bioconjugation
Hong, Vu; Presolski, Stanislav I.; Ma, Celia; Finn, M. G.
Angewandte Chemie, International Edition (2009), 48 (52), 9879-9883, S9879/1-S9879/10CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
Copper-catalyzed azide-alkyne cycloaddn. (CuAAC) has been optimized for use with biol. mols. The key development is the addn. of two reagents that allow ascorbate to be used as reducing agent while eliminating problems caused by copper ascorbate side reactions. The result is a robust, rapid, and convenient procedure for the modification of proteins, DNA, RNA, and other biomols. Sodium ascorbate is the preferred reducing agent for most applications, due to its convenience and effectiveness at generating the catalytically active Cu1 oxidn. state. Cu concns. should generally be between 50 and 100 μM. A fluorogenic or colorimetric assay, such as that enabled by a coumarin deriv. is strongly recommended for optimization of specific cases. At least five equiv. of THPTA (other water-sol. variants) relative to Cu should be employed. Aminoguanidine is a useful additive to intercept byproducts of ascorbate oxidn. that can covalently modify or crosslink proteins. Compatible buffers include phosphate, carbonate, or HEPES in the pH 6.5-8.0 range. Tris buffer should be avoided as it is a competitive and inhibitory ligand for Cu; sodium chloride (as in phosphate-buffered saline) up to 0.5 M can be used. Ascorbate should not be added to copper-contg. solns. in the absence of the ligand. As a matter of routine, the authors first mix CuSO4 with the ligand, add this mixt. to a soln. of the azide and alkyne substrates, and then initiate the CuAAC reaction by the addn. of sodium ascorbate to the desired concn. The Cu-THPTA catalyst in water is inhibited by excess alkyne, and so the procedure described here is useful for alkyne concns. less than approx. 5 mM.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXhsF2hsrnL&md5=2b85650bce37933080d02c417848f1e2
160
Kolodych, S.; Rasolofonjatovo, E.; Chaumontet, M.; Nevers, M.-C.; Créminon, C.; Taran, F. Angew. Chem., Int. Ed. 2013, 52, 12056
[ Crossref], [ PubMed], [ CAS], Google Scholar
160
Discovery of Chemoselective and Biocompatible Reactions Using a High-Throughput Immunoassay Screening
Kolodych, Sergii; Rasolofonjatovo, Evelia; Chaumontet, Manon; Nevers, Marie-Claire; Creminon, Christophe; Taran, Frederic
Angewandte Chemie, International Edition (2013), 52 (46), 12056-12060CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
A method for high-throughput screening for identification and optimization of potential "click" reactions, particularly dipolar cycloaddns., using an immunoassay is described. Reactive groups attached to either homovanillic amide or histamine groups were reacted on nanomolar scale with a variety of metal catalysts; treatment with surface-linked anti(homovanillamide) monoclonal antibodies and antihistamine monoclonal antibodies in soln. led to a color change only when cycloadducts (contg. both homovanillamide and histamine tags) were formed and immobilized on the surface. Reactions that generated product were then optimized using the same assay format; four of the reactions were then performed using nontagged substrates. A rhodium-catalyzed cycloaddns. of pyridiniumacetates to nitriles to form imidazolopyridinecarboxylates, an iridium-catalyzed cycloaddn. of benzyl azide with bromoalkynes to form bromo-1,2,3-triazoles, a palladium-catalyzed and copper-mediated oxidative Heck reaction of a phenylsydnone with alkenes to yield alkenylsydnones, and a copper-catalyzed cycloaddn. of arylsydnones with alkynes to form arylpyrazoles were discovered using this method. In particular, copper-catalyzed cycloaddn. of arylsydnones with alkynes to form arylpyrazoles was found to be applicable to a variety of biol. relevant substrates, was performed successfully in human blood plasma, and was used to label bovine serum albumin with a fluorescent tag.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhs1WmtbvF&md5=fd99fb5fdf15e10d8b9078ce2dc90491
161
Tam, A.; Arnold, U.; Soellner, M. B.; Raines, R. T. J. Am. Chem. Soc. 2007, 129, 12670
[ ACS Full Text ], [ CAS], Google Scholar
161
Protein Prosthesis: 1,5-Disubstituted[1,2,3]triazoles as cis-Peptide Bond Surrogates
Tam, Annie; Arnold, Ulrich; Soellner, Matthew B.; Raines, Ronald T.
Journal of the American Chemical Society (2007), 129 (42), 12670-12671CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
Here, 1,5-disubstituted[1,2,3]triazoles were assessed as cis-peptide bond surrogates. Ruthenium-catalyzed Huisgen's 1,3-dipolar cycloaddn. reaction of amino alkynes and azido acids was used to synthesize a variety of Xaa-1,5-triazole-Ala modules (Xaa = Asn, Ala) in moderate-to-high yields. Two of these modules, along with their 1,4-triazole regioisomers, were installed in a turn region of bovine pancreatic RNase (RNase A; 124 residues) by using expressed protein ligation. The resulting semisynthetic enzymes displayed full enzymic activity, indicating the maintenance of native structure. The 1,5-triazole surrogates instilled conformational stability that was comparable to that of Xaa-cis-Pro segments, whereas the 1,4-triazoles conferred markedly less stability. The stability conferred by both surrogates was independent of the Xaa residue, eliminating an uncertainty in protein design. The authors conclude that Xaa-1,5-triazole-Ala modules can serve as viable mimics of Xaa-cis-Pro segments. The possibility of synthesizing this surrogate by the ligation of fragments in situ and the emergence of biocompatible catalysts for that process portends its widespread use.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXhtFSmsLvK&md5=721929f0f64c5819562ad9e27209a82c
162
Li, J.; Chen, P. R. ChemBioChem 2012, 13, 1728
[ Crossref], [ PubMed], [ CAS], Google Scholar
162
Moving Pd-Mediated Protein Cross Coupling to Living Systems
Li, Jie; Chen, Peng R.
ChemBioChem (2012), 13 (12), 1728-1731CODEN: CBCHFX; ISSN:1439-4227. (Wiley-VCH Verlag GmbH & Co. KGaA)
A review.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XpvVeksLo%253D&md5=8c6c6d6e7d4d5d0b53124e91a4319a2e
163
Li, N.; Lim, R. K. V.; Edwardraja, S.; Lin, Q. J. Am. Chem. Soc. 2011, 133, 15316
[ ACS Full Text ], [ CAS], Google Scholar
163
Copper-Free Sonogashira Cross-Coupling for Functionalization of Alkyne-Encoded Proteins in Aqueous Medium and in Bacterial Cells
Li, Nan; Lim, Reyna K.-V.; Edwardraja, Selvakumar; Lin, Qing
Journal of the American Chemical Society (2011), 133 (39), 15316-15319CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
Bioorthogonal reactions suitable for functionalization of genetically or metabolically encoded alkynes, for example, copper-catalyzed azide-alkyne cycloaddn. reaction ("click chem."), have provided chem. tools to study biomol. dynamics and function in living systems. Despite its prominence in org. synthesis, copper-free Sonogashira cross-coupling reaction suitable for biol. applications has not been reported. In this work, the authors report the discovery of a robust aminopyrimidine-palladium(II) complex for copper-free Sonogashira cross-coupling that enables selective functionalization of a homopropargylglycine (HPG)-encoded ubiquitin protein in aq. medium. A wide range of arom. groups including fluorophores and fluorinated arom. compds. can be readily introduced into the HPG-contg. ubiquitin under mild conditions with good to excellent yields. The suitability of this reaction for functionalization of HPG-encoded ubiquitin in Escherichia coli was also demonstrated. The high efficiency of this new catalytic system should greatly enhance the utility of Sonogashira cross-coupling in bioorthogonal chem.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhtFOmsbbK&md5=80ce0c00b57ace6aee26caa4f5d6d19b
164
Lim, R. K. V.; Li, N.; Ramil, C. P.; Lin, Q. ACS Chem. Biol. 2014, 9, 2139
[ ACS Full Text ], [ CAS], Google Scholar
164
Fast and Sequence-Specific Palladium-Mediated Cross-Coupling Reaction Identified from Phage Display
Lim, Reyna K. V.; Li, Nan; Ramil, Carlo P.; Lin, Qing
ACS Chemical Biology (2014), 9 (9), 2139-2148CODEN: ACBCCT; ISSN:1554-8929. (American Chemical Society)
Fast and specific bioorthogonal reactions are highly desirable because they provide efficient tracking of biomols. that are present in low abundance and/or involved in fast dynamic process in living systems. Toward this end, classic strategy involves the optimization of substrate structures and reaction conditions in test tubes, testing their compatibility with biol. systems, devising synthetic biol. schemes to introduce the modified substrates into living cells or organisms, and finally validating the superior kinetics for enhanced capacity in tracking biomols. in vivo, a lengthy process often mired by unexpected results. Here, the authors report a streamlined approach in which the "microenvironment" of a bioorthogonal chem. reporter is exploited directly in biol. systems via phage-assisted interrogation of reactivity (PAIR) to optimize not only reaction kinetics but also specificity. Using the PAIR strategy, the authors identified a short alkyne-contg. peptide sequence showing fast kinetics (k2 = 13,000 ± 2000 M-1s-1) in a palladium-mediated cross-coupling reaction. Site-directed mutagenesis studies suggested that the residues surrounding the alkyne moiety facilitate the assembly of a key palladium-alkyne intermediate along the reaction pathway. When this peptide sequence was inserted into the extracellular domain of epidermal growth factor receptor (EGFR), this reactive sequence directed the specific labeling of EGFR in live mammalian cells.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtFCrur%252FM&md5=f4cf9c0c1ad66b7e5f26c164c3a56ae1
165
Hauke, S.; Best, M.; Schmidt, T. T.; Baalmann, M.; Krause, A.; Wombacher, R. Bioconjugate Chem. 2014, 25, 1632
[ ACS Full Text ], [ CAS], Google Scholar
165
Two-Step Protein Labeling Utilizing Lipoic Acid Ligase and Sonogashira Cross-Coupling
Hauke, Sebastian; Best, Marcel; Schmidt, Tobias T.; Baalmann, Mathis; Krause, Andre; Wombacher, Richard
Bioconjugate Chemistry (2014), 25 (9), 1632-1637CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
Labeling proteins in their natural settings with fluorescent proteins or protein tags often leads to problems. Despite the high specificity, these methods influence the natural functions due to the rather large size of the proteins used. Here the authors present a two-step labeling procedure for the attachment of various fluorescent probes to a small peptide sequence (13 amino acids) using enzyme-mediated peptide labeling in combination with palladium-catalyzed Sonogashira cross-coupling. The authors identified p-iodophenyl derivs. from a small library that can be covalently attached to a lysine residue within a specific 13-amino-acid peptide sequence by Escherichia coli lipoic acid ligase A (LplA). The derivatization with p-iodophenyl subsequently served as a reactive handle for bioorthogonal transition metal-catalyzed Sonogashira cross-coupling with alkyne-functionalized fluorophores on both the peptide as well as on the protein level. The authors' two-step labeling strategy combines high selectivity of enzyme-mediated labeling with the chemoselectivity of palladium-catalyzed Sonogashira cross-coupling.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsVSnsb%252FK&md5=9608ef7c5905f9956699d689adbf95be
166
Li, N.; Ramil, C. P.; Lim, R. K. V.; Lin, Q. ACS Chem. Biol. 2015, DOI: 10.1021/cb500649q
[ ACS Full Text ], Google Scholar
There is no corresponding record for this reference.
167
Li, J.; Lin, S.; Wang, J.; Jia, S.; Yang, M.; Hao, Z.; Zhang, X.; Chen, P. R. J. Am. Chem. Soc. 2013, 135, 7330
[ ACS Full Text ], [ CAS], Google Scholar
167
Ligand-Free Palladium-Mediated Site-Specific Protein Labeling Inside Gram-Negative Bacterial Pathogens
Li, Jie; Lin, Shixian; Wang, Jie; Jia, Shang; Yang, Maiyun; Hao, Ziyang; Zhang, Xiaoyu; Chen, Peng R.
Journal of the American Chemical Society (2013), 135 (19), 7330-7338CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
Palladium, a key transition metal in advancing modern org. synthesis, mediates diverse chem. conversions including many carbon-carbon bond formation reactions between org. compds. However, expanding palladium chem. for conjugation of biomols. such as proteins, particularly within their native cellular context, is still in its infancy. Here the authors report the site-specific protein labeling inside pathogenic Gram-neg. bacterial cells via a ligand-free palladium-mediated cross-coupling reaction. Two rationally designed pyrrolysine analogs bearing an aliph. alkyne or an iodophenyl handle were first encoded in different enteric bacteria, which offered two facial handles for palladium-mediated Sonogashira coupling reaction on proteins within these pathogens. A GFP-based bioorthogonal reaction screening system was then developed, allowing evaluation of both the efficiency and the biocompatibility of various palladium reagents in promoting protein-small mol. conjugation. The identified simple compd. Pd(NO3)2 exhibited high efficiency and biocompatibility for site-specific labeling of proteins in vitro and inside living E. coli cells. This Pd-mediated protein coupling method was further used to label and visualize a Type-III Secretion (T3S) toxin-OspF in Shigella cells. The authors' strategy may be generally applicable for imaging and tracking various virulence proteins within Gram-neg. bacterial pathogens.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXntVWru74%253D&md5=4aeebc12f2f7c19fe35cabc2500566bc
168
Li, J.; Yu, J.; Zhao, J.; Wang, J.; Zheng, S.; Lin, S.; Chen, L.; Yang, M.; Jia, S.; Zhang, X.; Chen, P. R. Nat. Chem. 2014, 6, 352
[ Crossref], [ PubMed], [ CAS], Google Scholar
168
Palladium-triggered deprotection chemistry for protein activation in living cells
Li, Jie; Yu, Juntao; Zhao, Jingyi; Wang, Jie; Zheng, Siqi; Lin, Shixian; Chen, Long; Yang, Maiyun; Jia, Shang; Zhang, Xiaoyu; Chen, Peng R.
Nature Chemistry (2014), 6 (4), 352-361CODEN: NCAHBB; ISSN:1755-4330. (Nature Publishing Group)
Employing small mols. or chem. reagents to modulate the function of an intracellular protein, particularly in a gain-of-function fashion, remains a challenge. In contrast to inhibitor-based loss-of-function approaches, methods based on a gain of function enable specific signalling pathways to be activated inside a cell. Here we report a chem. rescue strategy that uses a palladium-mediated deprotection reaction to activate a protein within living cells. We identify biocompatible and efficient palladium catalysts that cleave the propargyl carbamate group of a protected lysine analog to generate a free lysine. The lysine analog can be genetically and site-specifically incorporated into a protein, which enables control over the reaction site. This deprotection strategy is shown to work with a range of different cell lines and proteins. We further applied this biocompatible protection group/catalyst pair for caging and subsequent release of a crucial lysine residue in a bacterial Type III effector protein within host cells, which reveals details of its virulence mechanism.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXktlGntbo%253D&md5=31492f7589ae74bbf389b0400ddfa543
169
(a) Cheng, G.; Lim, R. K. V.; Li, N.; Lin, Q. Chem. Commun. 2013, 49, 6809
[ Crossref], [ PubMed], [ CAS], Google Scholar
169a
Storable palladacycles for selective functionalization of alkyne-containing proteins
Cheng, Gang; Lim, Reyna K. V.; Li, Nan; Lin, Qing
Chemical Communications (Cambridge, United Kingdom) (2013), 49 (60), 6809-6811CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
We report the facile prepn. of palladacycles as storable arylpalladium(II) reagents from acetanilides via cyclopalladation. The palladacycles exhibit good stability in PBS buffer and are capable of functionalizing a metabolically encoded HPG-contg. protein, thus providing a new type of biocompatible organometallic reagent for selectively functionalizing the alkyne-encoded proteins.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtVCqur%252FI&md5=1bccc5ddd5a69c1ae41f78941bdf304f
(b) Cheng, G.; Lim, R. K. V.; Ramil, C. P.; Lin, Q. Chem. Commun. 2014, 50, 11679
[ Crossref], [ PubMed], [ CAS], Google Scholar
169b
Storable N-phenylcarbamate palladacycles for rapid functionalization of an alkyne-encoded protein
Cheng, Gang; Lim, Reyna K. V.; Ramil, Carlo P.; Lin, Qing
Chemical Communications (Cambridge, United Kingdom) (2014), 50 (79), 11679-11682CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
Here the authors report the synthesis of storable N-phenylcarbamate palladacycles, e.g., [EtOC(O)NC6H4-2-Pd(OTs)]2, that showed robust reactivity in the cross-coupling reaction with an alkyne-encoded protein, e.g., homopropargylglycine-encoded ubiquitin (Ub-Hpg), with a 2nd-order rate const. approaching 19,770 ± 930 M-1 s-1.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtlahtLzI&md5=8829434fa4db0fd92383bedef800cb37
170
Lin, Y. A.; Chalker, J. M.; Davis, B. G. ChemBioChem 2009, 10, 959
[ Crossref], [ PubMed], [ CAS], Google Scholar
170
Olefin Metathesis for Site-Selective Protein Modification
Lin, Yuya A.; Chalker, Justin M.; Davis, Benjamin G.
ChemBioChem (2009), 10 (6), 959-969CODEN: CBCHFX; ISSN:1439-4227. (Wiley-VCH Verlag GmbH & Co. KGaA)
A review. Protein compatible olefin metathesis has emerged as a viable strategy for site-selective protein modification. This minireview traces its development from early peptide models and metathesis in water to its ultimate application to protein substrates. Prospects in chem. and biol. are also discussed. For a reaction to be generally useful for protein modification, it must be site-selective and efficient under conditions compatible with proteins: aq. media, low to ambient temp., and at or near neutral pH. To engineer a reaction that satisfies these conditions is not a simple task. Olefin metathesis is one of most useful reactions for carbon-carbon bond formation, but does it fit these requirements This minireview is an account of the development of olefin metathesis for protein modification. Highlighted below are examples of olefin metathesis in peptidic systems and in aq. media that laid the groundwork for successful metathesis on protein substrates. Also discussed are the opportunities in protein engineering for the genetic introduction of amino acids suitable for metathesis and the related challenges in chem. and biol.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXltVOlt7g%253D&md5=008e690219a6d333aabf7d43cc19e6f6
171
(a) Lin, Y. A.; Chalker, J. M.; Davis, B. G. J. Am. Chem. Soc. 2010, 132, 16805
[ ACS Full Text ], [ CAS], Google Scholar
171a
Olefin Cross-Metathesis on Proteins: Investigation of Allylic Chalcogen Effects and Guiding Principles in Metathesis Partner Selection
Lin, Yu-Ya A.; Chalker, Justin M.; Davis, Benjamin G.
Journal of the American Chemical Society (2010), 132 (47), 16805-16811CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
Olefin metathesis has recently emerged as a viable reaction for chem. protein modification. The scope and limitations of olefin metathesis in bioconjugation, however, remain unclear. Herein the authors report an assessment of various factors that contribute to productive cross-metathesis on protein substrates. Sterics, substrate scope, and linker selection are all considered. It was discovered during this investigation that allyl chalcogenides generally enhance the rate of alkene metathesis reactions. Allyl selenides were exceptionally reactive olefin metathesis substrates, enabling a broad range of protein modifications not previously possible. The principles considered in this report are important not only for expanding the repertoire of bioconjugation but also for the application of olefin metathesis in general synthetic endeavors.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhtlyhtb%252FI&md5=1467f980a2500218483ad3de98a19b53
(b) Lin, Y. A.; Chalker, J. M.; Floyd, N.; Bernardes, G. J. L.; Davis, B. G. J. Am. Chem. Soc. 2008, 130, 9642
[ ACS Full Text ], [ CAS], Google Scholar
171b
Allyl Sulfides Are Privileged Substrates in Aqueous Cross-Metathesis: Application to Site-Selective Protein Modification
Lin, Yuya A.; Chalker, Justin M.; Floyd, Nicola; Bernardes, Goncalo J. L.; Davis, Benjamin G.
Journal of the American Chemical Society (2008), 130 (30), 9642-9643CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
Allyl sulfides undergo efficient cross-metathesis in aq. media with Hoveyda-Grubbs second generation catalyst. The high reactivity of allyl sulfides in cross-metathesis was exploited in the first examples of cross-metathesis on a protein surface. S-Allylcysteine was incorporated chem. into the protein, providing the requisite allyl sulfide handle. Preliminary efforts to genetically incorporate S-allylcysteine into proteins are also reported.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXnvF2gs7Y%253D&md5=a5d1a713c0c13d80961804b3bbfd9585
172
Chalker, J. M.; Lin, Y. A.; Boutureira, O.; Davis, B. G. Chem. Commun. 2009, 3714
[ Crossref], [ PubMed], [ CAS], Google Scholar
172
Enabling olefin metathesis on proteins: chemical methods for installation of S-allyl cysteine
Chalker, Justin M.; Lin, Yuya A.; Boutureira, Omar; Davis, Benjamin G.
Chemical Communications (Cambridge, United Kingdom) (2009), (25), 3714-3716CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
Multiple, complementary methods are reported for the chem. conversion of cysteine to S-allylcysteine (Sac) on protein surfaces, a useful transformation for the exploration of olefin metathesis on proteins. These methods are the direct allylation of cysteine with allyl chloride and allylation by an allyl selenenyl sulfide rearrangement. The authors demonstrate that these methods are cysteine selective and provide metathesis-active Sac-contg. proteins. Moreover, the electrophilic allylation and allylic selenenyl sulfide rearrangement methods provide a single diastereomer of S-allylcysteine, unlike the nucleophilic addn. to dehydroalanine. Finally, the methods are mild, efficient, and easily accomplished without denaturing the protein.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXnslenu7g%253D&md5=fdd936e91817707c35f1f07ee1024d91
173
Lin, Y. A.; Davis, B. G. Beilstein J. Org. Chem. 2010, 6, 1219
[ Crossref], [ PubMed], [ CAS], Google Scholar
173
The allylic chalcogen effect in olefin metathesis
Lin, Yuya A.; Davis, Benjamin G.
Beilstein Journal of Organic Chemistry (2010), 6 (), 1219-1228, No. 140CODEN: BJOCBH; ISSN:1860-5397. (Beilstein-Institut zur Foerderung der Chemischen Wissenschaften)
A review. Olefin metathesis has emerged as a powerful tool in org. synthesis. The activating effect of an allylic hydroxy group in metathesis has been known for more than 10 years, and many org. chemists have taken advantage of this pos. influence for efficient synthesis of natural products. Recently, the discovery of the rate enhancement by allyl sulfides in aq. cross-metathesis has allowed the first examples of such a reaction on proteins. This led to a new benchmark in substrate complexity for cross-metathesis and expanded the potential of olefin metathesis for other applications in chem. biol. The enhanced reactivity of allyl sulfide, along with earlier reports of a similar effect by allylic hydroxy groups, suggests that allyl chalcogens generally play an important role in modulating the rate of olefin metathesis. In this review, we discuss the effect of allylic chalcogens in olefin metathesis and highlight its most recent applications in synthetic chem. and protein modifications.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXjtlWruw%253D%253D&md5=269675c0ff77266a15cb7e277e321651
174
Lin, Y. A.; Boutureira, O.; Lercher, L.; Bhushan, B.; Paton, R. S.; Davis, B. G. J. Am. Chem. Soc. 2013, 135, 12156
[ ACS Full Text ], [ CAS], Google Scholar
174
Rapid Cross-Metathesis for Reversible Protein Modifications via Chemical Access to Se-Allyl-selenocysteine in Proteins
Lin, Yuya A.; Boutureira, Omar; Lercher, Lukas; Bhushan, Bhaskar; Paton, Robert S.; Davis, Benjamin G.
Journal of the American Chemical Society (2013), 135 (33), 12156-12159CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
Cross-metathesis (CM) has recently emerged as a viable strategy for protein modification. Here, efficient protein CM has been demonstrated through biomimetic chem. access to Se-allyl selenocysteine (Seac), a metathesis-reactive amino acid substrate, via dehydroalanine. On-protein reaction kinetics reveal a rapid reaction with rate consts. of Seac-mediated-CM comparable or superior to off-protein rates of many current bioconjugations. This use of Se-relayed Seac CM on proteins has now enabled reactions with substrates (allyl GlcNAc, N-allyl acetamide) that were previously not possible for the corresponding sulfur analog. This CM strategy was applied to histone proteins to install a mimic of acetylated lysine (KAc, an epigenetic marker). The resulting synthetic H3 was successfully recognized by antibody that binds natural H3-K9Ac. Moreover, Cope-type selenoxide elimination allowed this putative marker (and function) to be chem. expunged, regenerating an H3 that can be rewritten to complete a chem. enabled "write (CM)-erase (ox)-rewrite (CM)" cycle.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtFOltr%252FL&md5=c2deb443d9e4d9db8f4040ff53c23943
175
Ai, H.-W.; Shen, W.; Brustad, E.; Schultz, P. G. Angew. Chem., Int. Ed. 2010, 49, 935
[ Crossref], [ PubMed], [ CAS], Google Scholar
175
Genetically encoded alkenes in yeast
Ai, Hui-wang; Shen, Weijun; Brustad, Eric; Schultz, Peter G.
Angewandte Chemie, International Edition (2010), 49 (5), 935-937, S935/1-S935/6CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
The authors developed new tRNA/aminoacyl tRNA synthetase pairs that make possible the genetic incorporation of several alkene-contg. unnatural amino acids into proteins in eukaryotic cells. The orthogonal tRNA/aaRS pairs were evolved in Saccharomyces cerevisiae.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhtVGmsbc%253D&md5=dce69bcfcfaa069a417ca6622b0e653d
176
Ourailidou, M. E.; van der Meer, J.-Y.; Baas, B.-J.; Jeronimus-Stratingh, M.; Gottumukkala, A. L.; Poelarends, G. J.; Minnaard, A. J.; Dekker, F. J. ChemBioChem 2014, 15, 209
[ Crossref], [ PubMed], [ CAS], Google Scholar
176
Aqueous Oxidative Heck Reaction as a Protein-Labeling Strategy
Ourailidou, Maria Eleni; van der Meer, Jan-Ytzen; Baas, Bert-Jan; Jeronimus-Stratingh, Margot; Gottumukkala, Aditya L.; Poelarends, Gerrit J.; Minnaard, Adriaan J.; Dekker, Frank J.
ChemBioChem (2014), 15 (2), 209-212CODEN: CBCHFX; ISSN:1439-4227. (Wiley-VCH Verlag GmbH & Co. KGaA)
An increasing no. of chem. reactions are being employed for bio-orthogonal ligation of detection labels to protein-bound functional groups. Several of these strategies, however, are limited in their application to pure proteins and are ineffective in complex biol. samples such as cell lysates. Here we present the palladium-catalyzed oxidative Heck reaction as a new and robust bio-orthogonal strategy for linking functionalized arylboronic acids to protein-bound alkenes in high yields and with excellent chemoselectivity even in the presence of complex protein mixts. from living cells. Advantageously, this reaction proceeds under aerobic conditions, whereas most other metal-catalyzed reactions require inert atm.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhvFOjtb%252FN&md5=6f915f26482ca3c5fb190e44f4dde824
177
Crich, D.; Subramanian, V.; Karatholuvhu, M. J. Org. Chem. 2009, 74, 9422
[ ACS Full Text ], [ CAS], Google Scholar
177
Silver-Mediated Allylic Disulfide Rearrangement for Conjugation of Thiols in Protic Media
Crich, David; Subramanian, Venkataraman; Karatholuvhu, Maheswaran
Journal of Organic Chemistry (2009), 74 (24), 9422-9427CODEN: JOCEAH; ISSN:0022-3263. (American Chemical Society)
Alkyl and aryl allyl disulfides are induced to undergo the desulfurative allylic rearrangement by silver nitrate in protic solvents at room temp., thereby removing the necessity for the use of phosphines as thiophilic reagents. The silver-mediated reaction functions at ambient temp. in protic solvents and in the absence of protecting groups.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXhsVWhsb7M&md5=18503822511d3f8a5a0dc2bbf0c5135a
178
Crich, D.; Zou, Y.; Brebion, F. J. Org. Chem. 2006, 71, 9172
[ ACS Full Text ], [ CAS], Google Scholar
178
Sigmatropic Rearrangements as Tools for Amino Acid and Peptide Modification: Application of the Allylic Sulfur Ylide Rearrangement to the Preparation of Neoglycoconjugates and Other Conjugates
Crich, David; Zou, Yekui; Brebion, Franck
Journal of Organic Chemistry (2006), 71 (24), 9172-9177CODEN: JOCEAH; ISSN:0022-3263. (American Chemical Society)
S-allyl and S-methallyl cysteines and cysteine-contg. dipeptide derivs. undergo ylide formation and [2,3] sigmatropic rearrangement reactions with stabilized and unstabilized diazo compds. and N-(diazoacetyl)glycosylamines in the presence of dirhodium tetraacetate to yield substituted S-allylated cysteines, cysteine-contg. peptides, and neoglycoconjugates such as I in 32-57% yields. Reaction of S-methallyl-Boc-L-Cys-L-Ala-L-Trp-OMe with Me(CH2)14COCHN2 gives a mixt. of products in low yield favoring insertion into the indole N-H bond.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28XhtFWju7nK&md5=ceb53807c5d8c03dbd6eedd40b343ab6
179
Croft, L. Nat. Chem. 2010, 2, 1009
[ Crossref], [ PubMed], [ CAS], Google Scholar
179
Prestige for palladium
Croft, Laura
Nature Chemistry (2010), 2 (12), 1009CODEN: NCAHBB; ISSN:1755-4330. (Nature Publishing Group)
There is no expanded citation for this reference.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhsVOrsL%252FE&md5=591096d81d6775ecd87af2b880d5519e
180
Ojida, A.; Tsutsumi, H.; Kasagi, N.; Hamachi, I. Tetrahedron Lett. 2005, 46, 3301
[ Crossref], [ CAS], Google Scholar
180
Suzuki coupling for protein modification
Ojida, Akio; Tsutsumi, Hiroshi; Kasagi, Noriyuki; Hamachi, Itaru
Tetrahedron Letters (2005), 46 (19), 3301-3305CODEN: TELEAY; ISSN:0040-4039. (Elsevier B.V.)
Suzuki-coupling, a representative cross-coupling reaction between small mols., can proceed on a protein surface in aq. soln. under mild conditions. The modified protein produced by the coupling reaction maintained its native like structure and function. In addn., fluorescent dye appended-protein acts as a fluorescent biosensor.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXjtlKgu7c%253D&md5=e10fe7b7863166675da4ab0f805bf302
181
Kodama, K.; Fukuzawa, S.; Nakayama, H.; Kigawa, T.; Sakamoto, K.; Yabuki, T.; Matsuda, N.; Shirouzu, M.; Takio, K.; Tachibana, K.; Yokoyama, S. ChemBioChem 2006, 7, 134
[ Crossref], [ PubMed], [ CAS], Google Scholar
181
Regioselective carbon-carbon bond formation in proteins with palladium catalysis; new protein chemistry by organometallic chemistry
Kodama, Koichiro; Fukuzawa, Seketsu; Nakayama, Hiroshi; Kigawa, Takanori; Sakamoto, Kensaku; Yabuki, Takashi; Matsuda, Natsuko; Shirouzu, Mikako; Takio, Koji; Tachibana, Kazuo; Yokoyama, Shigeyuki
ChemBioChem (2006), 7 (1), 134-139CODEN: CBCHFX; ISSN:1439-4227. (Wiley-VCH Verlag GmbH & Co. KGaA)
The authors have used a Mizoroki-Heck reaction for site-specific carbon-carbon bond formation in the Ras protein. This was performed by the following two steps: (1) the His6-fused Ras protein contg. 4-iodo-L-phenylalanine at position 32 (iF32-Ras-His) was prepd. by genetic engineering, and (2) the aryl iodide group on the iF32-Ras-His was coupled with vinylated biotin in the presence of a palladium catalyst. The biotinylation was confirmed by Western blotting and liq. chromatog.-mass spectrometry (LC-MS). The regioselectivity of the Mizoroki-Heck reaction was furthermore confirmed by LC-MS/MS anal. However, in addn. to the biotinylated product (bF32-Ras-His), a dehalogenated product (F32-Ras-His) was detected by LC-MS/MS. This dehalogenation resulted from the undesired termination of the Mizoroki-Heck reaction due to steric and electrostatic hindrance around residue 32. The biotinylated Ras showed binding activity for the Ras-binding domain as its downstream target, Raf-1, with no sign of decompn. This study is the first report of an application of organometallic chem. in protein chem.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28Xms1OmtQ%253D%253D&md5=cea92627c9ad74437baf24687f6acdb2
182
Kodama, K.; Fukuzawa, S.; Nakayama, H.; Sakamoto, K.; Kigawa, T.; Yabuki, T.; Matsuda, N.; Shirouzu, M.; Takio, K.; Yokoyama, S.; Tachibana, K. ChemBioChem 2007, 8, 232
[ Crossref], [ PubMed], [ CAS], Google Scholar
182
A new protein engineering approach combining chemistry and biology, part II, site-specific functionalization of proteins by organopalladium reactions
Kodama, Koichiro; Fukuzawa, Seketsu; Nakayama, Hiroshi; Sakamoto, Kensaku; Kigawa, Takanori; Yabuki, Takashi; Matsuda, Natsuko; Shirouzu, Mikako; Takio, Koji; Yokoyama, Shigeyuki; Tachibana, Kazuo
ChemBioChem (2007), 8 (2), 232-238CODEN: CBCHFX; ISSN:1439-4227. (Wiley-VCH Verlag GmbH & Co. KGaA)
A new carbon-carbon bond has been regio-selectively introduced into a target position (position 32 or 174) of the Ras protein by two types of organopalladium reactions (Mizoroki-Heck and Sonogashira reactions). Reaction conditions were screened by using a model peptide, and the stability of the Ras protein under the reaction conditions was examd. by using the wild-type Ras protein. Finally, the iF-Ras proteins contg. a 4-iodo-L-phenylalanine residue were subjected to organopalladium reactions with vinylated or propargylated biotin. Site-specific biotinylations of the Ras protein were confirmed by Western blot and LC-MS/MS.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXht1Gnu7g%253D&md5=1b9f4349dc1b8fde4a34aea200f6dd83
183
Brustad, E.; Bushey, M. L.; Lee, J. W.; Groff, D.; Liu, W.; Schultz, P. G. Angew. Chem., Int. Ed. 2008, 47, 8220
[ Crossref], [ PubMed], [ CAS], Google Scholar
183
A genetically encoded boronate-containing amino acid
Brustad, Eric; Bushey, Mark L.; Lee, Jae Wook; Groff, Dan; Liu, Wenshe; Schultz, Peter G.
Angewandte Chemie, International Edition (2008), 47 (43), 8220-8223CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
A biol. boronate: An orthogonal tRNA/aminoacyl-tRNA synthetase pair has been evolved for the genetic incorporation of a boronic acid into proteins. This amino acid has been used to purify proteins in a one-step scarless purifn. procedure as well as for the site-specific labeling of proteins using various boronic acid chemistries.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXht12htbrM&md5=049397eb711ad18bacd71746845d0acd
184
Chalker, J. M.; Wood, C. S. C.; Davis, B. G. J. Am. Chem. Soc. 2009, 131, 16346
[ ACS Full Text ], [ CAS], Google Scholar
184
A Convenient Catalyst for Aqueous and Protein Suzuki-Miyaura Cross-Coupling
Chalker, Justin M.; Wood, Charlotte S. C.; Davis, Benjamin G.
Journal of the American Chemical Society (2009), 131 (45), 16346-16347CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
A phosphine-free palladium catalyst, generated from base, 4,6-dihydroxy-2-aminopyrimidine, and palladium acetate (I), is used as a catalyst for aq. Suzuki-Miyaura cross-coupling reactions of iodophenyl- and bromophenyl-contg. amino acids, an iodobenzylated protein, and iodoarenes with aryl boronic acids and an alkenylboronate. I mediates Suzuki-Miyaura coupling reactions to give hindered, ortho-substituted biaryls but does not react with or decomp. either peptides and proteins. The catalyst mediates Suzuki-Miyaura coupling reactions of brominated and iodinated Boc-tyrosines and S-(4-iodobenzyl)-Boc-glutathione, but does not catalyze Suzuki-Miyaura coupling of S-(4-iodobenzyl)-Boc-L-cysteine with phenylboronic acid; free cysteine or glutathione inhibit coupling reactions in the presence of I. A mutant of subtilisin Bacillus lentus (with a cysteine at residue 154 replacing a serine) is iodobenzylated at cysteine 154 and deactivated by benzylsulfonylation of the active site serine at residue 215; the inactivated and iodobenzylated product undergoes couplings with a variety of boronic acids in the presence of I in water in >95% conversions. The Suzuki-Miyaura couplings on the protein substrate are the first on a protein to proceed in useful conversions. Hydrophobic aryl and vinyl groups can be transferred to the protein surface without the aid of an org. solvent since the aryl- and vinylboronic acids used in the coupling are water-sol. as borate salts. The convenience and activity of this catalyst prompts use in both general synthesis and bioconjugation.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXhtlSlsLvF&md5=98a5115c8b3ea7175c6534fdf078e4a0
185
Spicer, C. D.; Davis, B. G. Chem. Commun. 2011, 47, 1698
[ Crossref], [ PubMed], [ CAS], Google Scholar
185
Palladium-mediated site-selective Suzuki-Miyaura protein modification at genetically encoded aryl halides
Spicer, Christopher D.; Davis, Benjamin G.
Chemical Communications (Cambridge, United Kingdom) (2011), 47 (6), 1698-1700CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
Site-specific genetic incorporation of unnatural p-halophenylalanine amino acid residues as tags coupled with Pd(0)-mediated Suzuki-Miyuara modification has been enabled by discovery of an effective small mol. palladium scavenger.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXht1Wgs7s%253D&md5=265eee282a04f816f743c9cc3fe5de79
186
Spicer, C. D.; Triemer, T.; Davis, B. G. J. Am. Chem. Soc. 2012, 134, 800
[ ACS Full Text ], [ CAS], Google Scholar
186
Palladium-Mediated Cell-Surface Labeling
Spicer, Christopher D.; Triemer, Therese; Davis, Benjamin G.
Journal of the American Chemical Society (2012), 134 (2), 800-803CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
Benign C-C bond formation at various sites in cell-surface channels has been achieved through Suzuki-Miyaura coupling of genetically positioned unnatural amino acids contg. aryl halide side chains. This enabled site-selective cell surface manipulation of Escherichia coli; the phosphine-free catalyst caused no cell death at required Pd loadings, suggesting future in vivo application of catalytic metal-mediated bond formation in more complex organisms.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhs1ers7zK&md5=f82eea8977542b5a69751a523cbaa6c6
187
Spicer, C. D.; Davis, B. G. Chem. Commun. 2013, 49, 2747
[ Crossref], [ PubMed], [ CAS], Google Scholar
187
Rewriting the bacterial glycocalyx via Suzuki-Miyaura cross-coupling
Spicer, Christopher D.; Davis, Benjamin G.
Chemical Communications (Cambridge, United Kingdom) (2013), 49 (27), 2747-2749CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
Suzuki-Miyaura cross-coupling has been used to couple novel carbohydrate-based boronic acids, site-selectively, to the surface of E. coli at an unnatural amino acid. In this way, benign metal-catalyzed cellular switching allowed modulation of interactions with biomol. partners via prokaryotic O-glycosylation mimics.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXjslGntr4%253D&md5=2d6286f4710e8ee42ca04388d3851365
188
Ma, X.; Wang, H.; Chen, W. J. Org. Chem. 2014, 79, 8652
[ ACS Full Text ], [ CAS], Google Scholar
188
N-Heterocyclic Carbene-Stabilized Palladium Complexes as Organometallic Catalysts for Bioorthogonal Cross-Coupling Reactions
Ma, Xueji; Wang, Hangxiang; Chen, Wanzhi
Journal of Organic Chemistry (2014), 79 (18), 8652-8658CODEN: JOCEAH; ISSN:0022-3263. (American Chemical Society)
A small library of water-sol. N-heterocyclic carbene (NHC)-stabilized palladium complexes was prepd. and applied for cross-couplings of biomols. under mild conditions in water. Pd-NHC complexes bearing hydrophilic groups are efficient catalysts for the Suzuki-Miyaura coupling of various unnatural amino acids and proteins bearing p-iodophenyl functional groups. The authors further used this catalytic system for the rapid bioorthogonal labeling of proteins on the surfaces of mammalian cells. NHC-stabilized metal complexes have potential utility in cellular systems.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsVSns73J&md5=dc548e115000070b40b3a4c467d85fc3
189
Dumas, A.; Spicer, C. D.; Gao, Z.; Takehana, T.; Lin, Y. A.; Yasukohchi, T.; Davis, B. G. Angew. Chem., Int. Ed. 2013, 52, 3916
[ Crossref], [ PubMed], [ CAS], Google Scholar
189
Self-Liganded Suzuki-Miyaura Coupling for Site-Selective Protein PEGylation
Dumas, Anaelle; Spicer, Christopher D.; Gao, Zhanghua; Takehana, Tsuyoshi; Lin, Yuya A.; Yasukohchi, Tohru; Davis, Benjamin G.
Angewandte Chemie, International Edition (2013), 52 (14), 3916-3921CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
PEG-boronic acids, in the presence of simple Pd sources, are capable of acting as direct and effective Suzuki reagents in 70-98% yield. When combined with non-natural amino acids, they allow efficient and direct, site-selective PEGylation of proteins at predetd. positions under biol. compatible conditions without the need for exogenous ligands.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXjtVems7o%253D&md5=62a40ee8f1a8b5f5f2e4970c2d18add2

Cited By

This article is cited by 374 publications.

Shayan Abbasi, Homa Farahani, Hossein Lanjanian, Mohammad Taheri, Loghman Firoozpour, Jamshid Davoodi, Sama Pirkalkhoran, GholamHossein Riazi, Shahriar Pooyan. Site Directed Disulfide PEGylation of Interferon-β-1b with Fork Peptide Linker. Bioconjugate Chemistry 2020, Article ASAP.
Enric Ros, Marina Bellido, Xavier Verdaguer, Lluís Ribas de Pouplana, Antoni Riera. Synthesis and Application of 3-Bromo-1,2,4,5-Tetrazine for Protein Labeling to Trigger Click-to-Release Biorthogonal Reactions. Bioconjugate Chemistry 2020, Article ASAP.
Tae-Kyung Lee, Bikash Manandhar, Kara J. Kassees, Jung-Mo Ahn. Peptide Ligation via the Suzuki–Miyaura Cross-Coupling Reaction. The Journal of Organic Chemistry 2020, 85 (3) , 1376-1384. DOI: 10.1021/acs.joc.9b02313.
Jinhua Yang, Changliu Wang, Chaochao Yao, Chunqiu Chen, Yafang Hu, Guifeng He, Junfeng Zhao. Site-Specific Incorporation of Multiple Thioamide Substitutions into a Peptide Backbone via Solid Phase Peptide Synthesis. The Journal of Organic Chemistry 2020, 85 (3) , 1484-1494. DOI: 10.1021/acs.joc.9b02486.
Hailey A. Young, Quibria A. E. Guthrie, Caroline Proulx. N-Arylation of Amino Acid Esters to Expand Side Chain Diversity in Ketoxime Peptide Ligations. The Journal of Organic Chemistry 2020, 85 (3) , 1748-1755. DOI: 10.1021/acs.joc.9b02810.
Teruyuki Miyake, Ryosei Tamaki, Moeko Asanuma, Yoji Fukada, Shun Hirota, Takashi Matsuo. Regioselective Chemical Modification of Cysteine Residues on Protein Surfaces Focusing on Local Environment around the Conjugation Site. Bioconjugate Chemistry 2020, Article ASAP.
Qing Zhang, Yue Zhang, Heng Liu, Hoi Yee Chow, Ruijun Tian, Yi Man Eva Fung, Xuechen Li. OPA-Based Bifunctional Linker for Protein Labeling and Profiling. Biochemistry 2020, 59 (2) , 175-178. DOI: 10.1021/acs.biochem.9b00787.
Jia Zang, Yulin Chen, Wenxuan Zhu, Shixian Lin. Chemoselective Methionine Bioconjugation on a Polypeptide, Protein, and Proteome. Biochemistry 2020, 59 (2) , 132-138. DOI: 10.1021/acs.biochem.9b00789.
Vincenzo Mangini, Vito Maggi, Alberta Trianni, Francesca Melle, Elisa De Luca, Antonio Pennetta, Roberta Del Sole, Giovanni Ventura, Tommaso R. I. Cataldi, Roberto Fiammengo. Directional Immobilization of Proteins on Gold Nanoparticles Is Essential for Their Biological Activity: Leptin as a Case Study. Bioconjugate Chemistry 2020, 31 (1) , 74-81. DOI: 10.1021/acs.bioconjchem.9b00748.
Caroline Apel, Marc-André Kasper, Christian E. Stieger, Christian P. R. Hackenberger, Mathias Christmann. Protein Modification of Lysine with 2-(2-Styrylcyclopropyl)ethanal. Organic Letters 2019, 21 (24) , 10043-10047. DOI: 10.1021/acs.orglett.9b03982.
Stefanie L. Baker, Bibifatima Kaupbayeva, Sushil Lathwal, Subha R. Das, Alan J. Russell, Krzysztof Matyjaszewski. Atom Transfer Radical Polymerization for Biorelated Hybrid Materials. Biomacromolecules 2019, 20 (12) , 4272-4298. DOI: 10.1021/acs.biomac.9b01271.
Robert E. Thompson, Tom W. Muir. Chemoenzymatic Semisynthesis of Proteins. Chemical Reviews 2019, Article ASAP.
Nicholas David James Yates, Mark R Dowsett, Phillip Bentley, Jack A Dickenson-Fogg, Andrew Pratt, Christopher Francis Blanford, Martin Fascione, Alison Parkin. Aldehyde-mediated protein-to-surface tethering via controlled diazonium electrode functionalization using protected hydroxylamines. Langmuir , 0 (ja) DOI: 10.1021/acs.langmuir.9b01254.
Jin Chang, Weiqi Cai, Chunjing Liang, Qiao Tang, Xianghan Chen, Ying Jiang, Lanqun Mao, Ming Wang. Enzyme-Instructed Activation of Pro-protein Therapeutics In Vivo. Journal of the American Chemical Society 2019, 141 (45) , 18136-18141. DOI: 10.1021/jacs.9b08669.
Xiaoping Chen, Farong Ye, Xiaosheng Luo, Xueyi Liu, Jie Zhao, Siyao Wang, Qingqing Zhou, Gong Chen, Ping Wang. Histidine-Specific Peptide Modification via Visible-Light-Promoted C–H Alkylation. Journal of the American Chemical Society 2019, 141 (45) , 18230-18237. DOI: 10.1021/jacs.9b09127.
Di Wang, Peifeng Lv, Liang Zhang, Shuqiao Yang, Yanxiang Gao. Structural and Functional Characterization of Laccase-Induced β-Lactoglobulin–Ferulic Acid–Chitosan Ternary Conjugates. Journal of Agricultural and Food Chemistry 2019, 67 (43) , 12054-12060. DOI: 10.1021/acs.jafc.9b04557.
Fabian B. H. Rehm, Thibault J. Harmand, Kuok Yap, Thomas Durek, David J. Craik, Hidde L. Ploegh. Site-Specific Sequential Protein Labeling Catalyzed by a Single Recombinant Ligase. Journal of the American Chemical Society 2019, 141 (43) , 17388-17393. DOI: 10.1021/jacs.9b09166.
Byungjin Koo, Nicholas S. Dolan, Kristin Wucherer, Henrik K. Munch, Matthew B. Francis. Site-Selective Protein Immobilization on Polymeric Supports through N-Terminal Imidazolidinone Formation. Biomacromolecules 2019, 20 (10) , 3933-3939. DOI: 10.1021/acs.biomac.9b01002.
Kohei Takemoto, Yasuhiro Nishikawa, Shohei Moriguchi, Yuna Hori, Yuki Kamezawa, Takami Matsui, Osamu Hara. Site-Selective Esterifications of Polyol β-Hydroxyamides and Applications to Serine-Selective Glycopeptide Modifications. Organic Letters 2019, 21 (18) , 7534-7538. DOI: 10.1021/acs.orglett.9b02809.
Thomas Schlatzer, Julia Kriegesmann, Hilmar Schröder, Melanie Trobe, Christian Lembacher-Fadum, Simone Santner, Alexander V. Kravchuk, Christian F. W. Becker, Rolf Breinbauer. Labeling and Natural Post-Translational Modification of Peptides and Proteins via Chemoselective Pd-Catalyzed Prenylation of Cysteine. Journal of the American Chemical Society 2019, 141 (37) , 14931-14937. DOI: 10.1021/jacs.9b08279.
Jorick J. Bruins, Criss van de Wouw, Koen Wagner, Lina Bartels, Bauke Albada, Floris L. van Delft. Highly Efficient Mono-Functionalization of Knob-in-Hole Antibodies with Strain-Promoted Click Chemistry. ACS Omega 2019, 4 (7) , 11801-11807. DOI: 10.1021/acsomega.9b01727.
Maryam Habibian, Willem A. Velema, Anna M. Kietrys, Yoshiyuki Onishi, Eric T. Kool. Polyacetate and Polycarbonate RNA: Acylating Reagents and Properties. Organic Letters 2019, 21 (14) , 5413-5416. DOI: 10.1021/acs.orglett.9b01526.
Hongli Yin, Dan Lu, Siyao Wang, Ping Wang. Development of Powerful Auxiliary-Mediated Ligation To Facilitate Rapid Protein Assembly. Organic Letters 2019, 21 (13) , 5138-5142. DOI: 10.1021/acs.orglett.9b01737.
Matthias Gehringer, Stefan A. Laufer. Emerging and Re-Emerging Warheads for Targeted Covalent Inhibitors: Applications in Medicinal Chemistry and Chemical Biology. Journal of Medicinal Chemistry 2019, 62 (12) , 5673-5724. DOI: 10.1021/acs.jmedchem.8b01153.
Junfeng Chen, Jiang Wang, Ke Li, Yuhan Wang, Martin Gruebele, Andrew L. Ferguson, Steven C. Zimmerman. Polymeric “Clickase” Accelerates the Copper Click Reaction of Small Molecules, Proteins, and Cells. Journal of the American Chemical Society 2019, 141 (24) , 9693-9700. DOI: 10.1021/jacs.9b04181.
Nicholas D. J. Yates, Robin L. Brabham, Richard J. Spears, Tessa Keenan, Philip A. Helliwell, David S. Pugh, Alison Parkin, Glenn A. Hurst, Martin A. Fascione. Chemical Bioconjugation of Proteins in an Undergraduate Lab: One-Pot Oxidation and Derivatization of the N-Terminus. Journal of Chemical Education 2019, 96 (6) , 1245-1249. DOI: 10.1021/acs.jchemed.8b00787.
Michelle K. Quinn, Susan James, Jennifer J. McManus. Chemical Modification Alters Protein–Protein Interactions and Can Lead to Lower Protein Solubility. The Journal of Physical Chemistry B 2019, 123 (20) , 4373-4379. DOI: 10.1021/acs.jpcb.9b02368.
Yuanwei Dai, Jiaping Weng, Justin George, Huan Chen, Qishan Lin, Jun Wang, Maksim Royzen, Qiang Zhang. Three-Component Protein Modification Using Mercaptobenzaldehyde Derivatives. Organic Letters 2019, 21 (10) , 3828-3833. DOI: 10.1021/acs.orglett.9b01294.
Shang Jia, Dan He, Christopher J. Chang. Bioinspired Thiophosphorodichloridate Reagents for Chemoselective Histidine Bioconjugation. Journal of the American Chemical Society 2019, 141 (18) , 7294-7301. DOI: 10.1021/jacs.8b11912.
Sobhana Babu Boga, Shane W. Krska, Songnian Lin, Dmitri Pissarnitski, Lin Yan, Ahmet Kekec, Weijuan Tang, Nicholas A. Pierson, Christopher A. Strulson, Eric Streckfuss, Xiaohong Zhu, Xiaoping Zhang, Terri Kelly, Craig A. Parish. Site-Selective Synthesis of Insulin Azides and Bioconjugates. Bioconjugate Chemistry 2019, 30 (4) , 1127-1132. DOI: 10.1021/acs.bioconjchem.9b00069.
James S. Italia, Partha Sarathi Addy, Sarah B. Erickson, Jennifer C. Peeler, Eranthie Weerapana, Abhishek Chatterjee. Mutually Orthogonal Nonsense-Suppression Systems and Conjugation Chemistries for Precise Protein Labeling at up to Three Distinct Sites. Journal of the American Chemical Society 2019, 141 (15) , 6204-6212. DOI: 10.1021/jacs.8b12954.
Lindsey C. Szymczak, Milan Mrksich. Using Peptide Arrays To Discover the Sequence-Specific Acetylation of the Histidine-Tyrosine Dyad. Biochemistry 2019, 58 (13) , 1810-1817. DOI: 10.1021/acs.biochem.9b00022.
Robert Chapman, Martina H. Stenzel. All Wrapped up: Stabilization of Enzymes within Single Enzyme Nanoparticles. Journal of the American Chemical Society 2019, 141 (7) , 2754-2769. DOI: 10.1021/jacs.8b10338.
Tomonori Tamura, Itaru Hamachi. Chemistry for Covalent Modification of Endogenous/Native Proteins: From Test Tubes to Complex Biological Systems. Journal of the American Chemical Society 2019, 141 (7) , 2782-2799. DOI: 10.1021/jacs.8b11747.
Sivaramapanicker Sreejith, Rahul Kishor, Ata Abbas, Rijil Thomas, Trifanny Yeo, Vivek Damodar Ranjan, Ramanathan Vaidyanathan, Yen Peng Seah, Bengang Xing, Zhenfeng Wang, Li Zeng, Yuanjin Zheng, Chwee Teck Lim. Nanomechanical Microfluidic Mixing and Rapid Labeling of Silica Nanoparticles using Allenamide-Thiol Covalent Linkage for Bioimaging. ACS Applied Materials & Interfaces 2019, 11 (5) , 4867-4875. DOI: 10.1021/acsami.8b20315.
Xiaoni Fang, Yongzan Zheng, Yaokai Duan, Yang Liu, Wenwan Zhong. Recent Advances in Design of Fluorescence-Based Assays for High-Throughput Screening. Analytical Chemistry 2019, 91 (1) , 482-504. DOI: 10.1021/acs.analchem.8b05303.
Feng Zhu, Eric Miller, Shuo-qing Zhang, Duk Yi, Sloane O’Neill, Xin Hong, Maciej A. Walczak. Stereoretentive C(sp3)–S Cross-Coupling. Journal of the American Chemical Society 2018, 140 (51) , 18140-18150. DOI: 10.1021/jacs.8b11211.
Xiaobao Bi, Juan Yin, Chang Rao, Seetharamsing Balamkundu, Biplab Banerjee, Dingpeng Zhang, Dawei Zhang, Peter C. Dedon, Chuan-Fa Liu. Thiazolidin-5-imine Formation as a Catalyst-Free Bioorthogonal Reaction for Protein and Live Cell Labeling. Organic Letters 2018, 20 (24) , 7790-7793. DOI: 10.1021/acs.orglett.8b03195.
Mari Takahara, Rie Wakabayashi, Kosuke Minamihata, Masahiro Goto, Noriho Kamiya. Design of Lipid–Protein Conjugates Using Amphiphilic Peptide Substrates of Microbial Transglutaminase. ACS Applied Bio Materials 2018, 1 (6) , 1823-1829. DOI: 10.1021/acsabm.8b00271.
Jean B. Bertoldo, Hernán Terenzi, Stefan Hüttelmaier, Gonçalo J. L. Bernardes. Posttranslational Chemical Mutagenesis: To Reveal the Role of Noncatalytic Cysteine Residues in Pathogenic Bacterial Phosphatases. Biochemistry 2018, 57 (43) , 6144-6152. DOI: 10.1021/acs.biochem.8b00639.
Rong Huang, Zhihong Li, Yao Sheng, Jianghui Yu, Yue Wu, Yuexiong Zhan, Hongli Chen, Biao Jiang. N-Methyl-N-phenylvinylsulfonamides for Cysteine-Selective Conjugation. Organic Letters 2018, 20 (20) , 6526-6529. DOI: 10.1021/acs.orglett.8b02849.
Xiaohong Tan, Chuan-Fa Liu. Investigating Glyoxylate-Mediated Transamination Using Dipeptide Arrays and Proteomic Peptide Mixtures. Bioconjugate Chemistry 2018, 29 (10) , 3285-3292. DOI: 10.1021/acs.bioconjchem.8b00475.
Thibault J. Harmand, Djenet Bousbaine, Alix Chan, Xiaohong Zhang, David R. Liu, James P. Tam, Hidde L. Ploegh. One-Pot Dual Labeling of IgG 1 and Preparation of C-to-C Fusion Proteins Through a Combination of Sortase A and Butelase 1. Bioconjugate Chemistry 2018, 29 (10) , 3245-3249. DOI: 10.1021/acs.bioconjchem.8b00563.
R. Adam Aycock, Cameron J. Pratt, Nathan T. Jui. Aminoalkyl Radicals as Powerful Intermediates for the Synthesis of Unnatural Amino Acids and Peptides. ACS Catalysis 2018, 8 (10) , 9115-9119. DOI: 10.1021/acscatal.8b03031.
Dustin Kaiser, Johan M. Winne, Maria Elena Ortiz-Soto, Jürgen Seibel, Thien A. Le, Bernd Engels. Mechanistical Insights into the Bioconjugation Reaction of Triazolinediones with Tyrosine. The Journal of Organic Chemistry 2018, 83 (17) , 10248-10260. DOI: 10.1021/acs.joc.8b01445.
Christopher D. Spicer, E. Thomas Pashuck, Molly M. Stevens. Achieving Controlled Biomolecule–Biomaterial Conjugation. Chemical Reviews 2018, 118 (16) , 7702-7743. DOI: 10.1021/acs.chemrev.8b00253.
Maksymilian Marek Zegota, Tao Wang, Christiane Seidler, David Yuen Wah Ng, Seah Ling Kuan, Tanja Weil. “Tag and Modify” Protein Conjugation with Dynamic Covalent Chemistry. Bioconjugate Chemistry 2018, 29 (8) , 2665-2670. DOI: 10.1021/acs.bioconjchem.8b00358.
Xiaobao Bi, Juan Yin, Xinya Hemu, Chang Rao, James P. Tam, Chuan-Fa Liu. Immobilization and Intracellular Delivery of Circular Proteins by Modifying a Genetically Incorporated Unnatural Amino Acid. Bioconjugate Chemistry 2018, 29 (7) , 2170-2175. DOI: 10.1021/acs.bioconjchem.8b00244.
Adarshi P. Welegedara, Luke A. Adams, Thomas Huber, Bim Graham, Gottfried Otting. Site-Specific Incorporation of Selenocysteine by Genetic Encoding as a Photocaged Unnatural Amino Acid. Bioconjugate Chemistry 2018, 29 (7) , 2257-2264. DOI: 10.1021/acs.bioconjchem.8b00254.
Yunfei Wu, Jiulong Hu, Chen Sun, Yu Cao, Yuanhe Li, Fayang Xie, Tianyin Zeng, Bing Zhou, Juanjuan Du, Yefeng Tang. Nature-Inspired Bioorthogonal Reaction: Development of β-Caryophyllene as a Chemical Reporter in Tetrazine Ligation. Bioconjugate Chemistry 2018, 29 (7) , 2287-2295. DOI: 10.1021/acs.bioconjchem.8b00283.
Marco S. Messina, Julia M. Stauber, Mary A. Waddington, Arnold L. Rheingold, Heather D. Maynard, Alexander M. Spokoyny. Organometallic Gold(III) Reagents for Cysteine Arylation. Journal of the American Chemical Society 2018, 140 (23) , 7065-7069. DOI: 10.1021/jacs.8b04115.
Younong Yu, Li-Kang Zhang, Alexei V. Buevich, Guoqing Li, Haiqun Tang, Petr Vachal, Steven L. Colletti, Zhi-Cai Shi. Chemoselective Peptide Modification via Photocatalytic Tryptophan β-Position Conjugation. Journal of the American Chemical Society 2018, 140 (22) , 6797-6800. DOI: 10.1021/jacs.8b03973.
Christopher Jay T. Robidillo, Muhammad Amirul Islam, Maryam Aghajamali, Angelique Faramus, Regina Sinelnikov, Xiyu Zhang, Job Boekhoven, Jonathan G. C. Veinot. Functional Bioinorganic Hybrids from Enzymes and Luminescent Silicon-Based Nanoparticles. Langmuir 2018, 34 (22) , 6556-6569. DOI: 10.1021/acs.langmuir.8b01119.
Feiran Xu, Jing Zhang, Zhigao Wang, Yijun Yao, Griffiths G Atungulu, Xingrong Ju, Lifeng Wang. Absorption and Metabolism of Peptide WDHHAPQLR Derived from Rapeseed Protein and Inhibition of HUVEC Apoptosis under Oxidative Stress. Journal of Agricultural and Food Chemistry 2018, 66 (20) , 5178-5189. DOI: 10.1021/acs.jafc.8b01620.
Iván Ramos-Tomillero, Gema Perez-Chacon, Beatriz Somovilla-Crespo, Francisco Sanchez-Madrid, Juan Manuel Domínguez, Carmen Cuevas, Juan Manuel Zapata, Hortensia Rodríguez, Fernando Albericio. Bioconjugation through Mesitylene Thiol Alkylation. Bioconjugate Chemistry 2018, 29 (4) , 1199-1208. DOI: 10.1021/acs.bioconjchem.7b00828.
Peng An, Tracey M. Lewandowski, Tuğçe G. Erbay, Peng Liu, Qing Lin. Sterically Shielded, Stabilized Nitrile Imine for Rapid Bioorthogonal Protein Labeling in Live Cells. Journal of the American Chemical Society 2018, 140 (14) , 4860-4868. DOI: 10.1021/jacs.8b00126.
Naganaboina Naveen, Saumitra Sengupta, Srinivasan Chandrasekaran. Metal-Free S-Arylation of Cysteine Using Arenediazonium Salts. The Journal of Organic Chemistry 2018, 83 (7) , 3562-3569. DOI: 10.1021/acs.joc.7b03160.
Maria J. Matos, Bruno L. Oliveira, Nuria Martínez-Sáez, Ana Guerreiro, Pedro M. S. D. Cal, Jean Bertoldo, María Maneiro, Elizabeth Perkins, Julie Howard, Michael J. Deery, Justin M. Chalker, Francisco Corzana, Gonzalo Jiménez-Osés, Gonçalo J. L. Bernardes. Chemo- and Regioselective Lysine Modification on Native Proteins. Journal of the American Chemical Society 2018, 140 (11) , 4004-4017. DOI: 10.1021/jacs.7b12874.
Christopher J. White and Jeffrey W. Bode . PEGylation and Dimerization of Expressed Proteins under Near Equimolar Conditions with Potassium 2-Pyridyl Acyltrifluoroborates. ACS Central Science 2018, 4 (2) , 197-206. DOI: 10.1021/acscentsci.7b00432.
Stefan Borsley and Scott L. Cockroft . In Situ Synthetic Functionalization of a Transmembrane Protein Nanopore. ACS Nano 2018, 12 (1) , 786-794. DOI: 10.1021/acsnano.7b08105.
Bikram Keshari Agrawalla, Tao Wang, Andreas Riegger, Matthias P. Domogalla, Kerstin Steinbrink, Thilo Dörfler, Xi Chen, Felix Boldt, Markus Lamla, Jens Michaelis, Seah Ling Kuan, Tanja Weil. Chemoselective Dual Labeling of Native and Recombinant Proteins. Bioconjugate Chemistry 2018, 29 (1) , 29-34. DOI: 10.1021/acs.bioconjchem.7b00675.
Erika M. Milczek . Commercial Applications for Enzyme-Mediated Protein Conjugation: New Developments in Enzymatic Processes to Deliver Functionalized Proteins on the Commercial Scale. Chemical Reviews 2018, 118 (1) , 119-141. DOI: 10.1021/acs.chemrev.6b00832.
Clive L. Baveghems, Murali Anuganti, Ajith Pattammattel, Yao Lin, and Challa V. Kumar . Tuning Enzyme/α-Zr(IV) Phosphate Nanoplate Interactions via Chemical Modification of Glucose Oxidase. Langmuir 2018, 34 (1) , 480-491. DOI: 10.1021/acs.langmuir.7b02919.
Allyson M. Freedy, Maria J. Matos, Omar Boutureira, Francisco Corzana, Ana Guerreiro, Padma Akkapeddi, Víctor J. Somovilla, Tiago Rodrigues, Karl Nicholls, Bangwen Xie, Gonzalo Jiménez-Osés, Kevin M. Brindle, André A. Neves, and Gonçalo J. L. Bernardes . Chemoselective Installation of Amine Bonds on Proteins through Aza-Michael Ligation. Journal of the American Chemical Society 2017, 139 (50) , 18365-18375. DOI: 10.1021/jacs.7b10702.
Jitka Dadová, Kuan-Jung Wu, Patrick G. Isenegger, James C. Errey, Gonçalo J. L. Bernardes, Justin M. Chalker, Lluís Raich, Carme Rovira, and Benjamin G. Davis . Precise Probing of Residue Roles by Post-Translational β,γ-C,N Aza-Michael Mutagenesis in Enzyme Active Sites. ACS Central Science 2017, 3 (11) , 1168-1173. DOI: 10.1021/acscentsci.7b00341.
Qi Wang, Chun Zhang, Fangxia Guo, Zenglan Li, Yongdong Liu, and Zhiguo Su . Novel Bioconjugation Strategy Using Elevated Hydrostatic Pressure: A Case Study for the Site-Specific Attachment of Polyethylene Glycol (PEGylation) of Recombinant Human Ciliary Neurotrophic Factor. Bioconjugate Chemistry 2017, 28 (11) , 2841-2848. DOI: 10.1021/acs.bioconjchem.7b00531.
Marcos San Segundo, Itziar Guerrero, and Arkaitz Correa . Co-Catalyzed C(sp3)–H Oxidative Coupling of Glycine and Peptide Derivatives. Organic Letters 2017, 19 (19) , 5288-5291. DOI: 10.1021/acs.orglett.7b02567.
Chen Wang, Yuan-Ye Jiang, and Chen-Ze Qi . Mechanism and Origin of Chemical Selectivity in Oxaziridine-Based Methionine Modification: A Computational Study. The Journal of Organic Chemistry 2017, 82 (18) , 9765-9772. DOI: 10.1021/acs.joc.7b02026.
Zhihong Li, Rong Huang, Hongtao Xu, Jiakang Chen, Yuexiong Zhan, Xianhao Zhou, Hongli Chen, and Biao Jiang . Divinylsulfonamides as Specific Linkers for Stapling Disulfide Bonds in Peptides. Organic Letters 2017, 19 (18) , 4972-4975. DOI: 10.1021/acs.orglett.7b02464.
Woo Gyum Kim, Mi Eun Kang, Jae Bin Lee, Min Ho Jeon, Sungmin Lee, Jungha Lee, Bongseo Choi, Pedro M. S. D. Cal, Sebyung Kang, Jung-Min Kee, Gonçalo J. L. Bernardes, Jan-Uwe Rohde, Wonyoung Choe, and Sung You Hong . Nickel-Catalyzed Azide–Alkyne Cycloaddition To Access 1,5-Disubstituted 1,2,3-Triazoles in Air and Water. Journal of the American Chemical Society 2017, 139 (35) , 12121-12124. DOI: 10.1021/jacs.7b06338.
Anthony J. Rojas, Bradley L. Pentelute, and Stephen L. Buchwald . Water-Soluble Palladium Reagents for Cysteine S-Arylation under Ambient Aqueous Conditions. Organic Letters 2017, 19 (16) , 4263-4266. DOI: 10.1021/acs.orglett.7b01911.
Miao Liu, Zeyang Ji, Mingjie Zhang, and Jiang Xia . Versatile Site-Selective Protein Reaction Guided by WW Domain–Peptide Motif Interaction. Bioconjugate Chemistry 2017, 28 (8) , 2199-2205. DOI: 10.1021/acs.bioconjchem.7b00334.
Justine N. deGruyter, Lara R. Malins, and Phil S. Baran . Residue-Specific Peptide Modification: A Chemist’s Guide. Biochemistry 2017, 56 (30) , 3863-3873. DOI: 10.1021/acs.biochem.7b00536.
Thimmalapura M. Vishwanatha, Enrico Bergamaschi, and Alexander Dömling . Sulfur-Switch Ugi Reaction for Macrocyclic Disulfide-Bridged Peptidomimetics. Organic Letters 2017, 19 (12) , 3195-3198. DOI: 10.1021/acs.orglett.7b01324.
Stephanie A. Fisher, Alexander E.G. Baker, and Molly S. Shoichet . Designing Peptide and Protein Modified Hydrogels: Selecting the Optimal Conjugation Strategy. Journal of the American Chemical Society 2017, 139 (22) , 7416-7427. DOI: 10.1021/jacs.7b00513.
Wenjun Zhao, Hong Geun Lee, Stephen L. Buchwald, and Jacob M. Hooker . Direct 11CN-Labeling of Unprotected Peptides via Palladium-Mediated Sequential Cross-Coupling Reactions. Journal of the American Chemical Society 2017, 139 (21) , 7152-7155. DOI: 10.1021/jacs.7b02761.
Yingqian Zhang, Xiaoping Zhou, Yonghui Xie, Marc M. Greenberg, Zhen Xi, and Chuanzheng Zhou . Thiol Specific and Tracelessly Removable Bioconjugation via Michael Addition to 5-Methylene Pyrrolones. Journal of the American Chemical Society 2017, 139 (17) , 6146-6151. DOI: 10.1021/jacs.7b00670.
Adel M. ElSohly, James I. MacDonald, Nina B. Hentzen, Ioana L. Aanei, Kareem M. El Muslemany, and Matthew B. Francis . ortho-Methoxyphenols as Convenient Oxidative Bioconjugation Reagents with Application to Site-Selective Heterobifunctional Cross-Linkers. Journal of the American Chemical Society 2017, 139 (10) , 3767-3773. DOI: 10.1021/jacs.6b12966.
Jun Liu, Qingqing Chen, and Sharon Rozovsky . Utilizing Selenocysteine for Expressed Protein Ligation and Bioconjugations. Journal of the American Chemical Society 2017, 139 (9) , 3430-3437. DOI: 10.1021/jacs.6b10991.
Justin M. Lopchuk, Kasper Fjelbye, Yu Kawamata, Lara R. Malins, Chung-Mao Pan, Ryan Gianatassio, Jie Wang, Liher Prieto, James Bradow, Thomas A. Brandt, Michael R. Collins, Jeff Elleraas, Jason Ewanicki, William Farrell, Olugbeminiyi O. Fadeyi, Gary M. Gallego, James J. Mousseau, Robert Oliver, Neal W. Sach, Jason K. Smith, Jillian E. Spangler, Huichin Zhu, Jinjiang Zhu, and Phil S. Baran . Strain-Release Heteroatom Functionalization: Development, Scope, and Stereospecificity. Journal of the American Chemical Society 2017, 139 (8) , 3209-3226. DOI: 10.1021/jacs.6b13229.
Xiaobao Bi, Kalyan Kumar Pasunooti, Julien Lescar, and Chuan-Fa Liu . Thiazolidine-Masked α-Oxo Aldehyde Functionality for Peptide and Protein Modification. Bioconjugate Chemistry 2017, 28 (2) , 325-329. DOI: 10.1021/acs.bioconjchem.6b00667.
Nancy L. Benner, Xiaoyu Zang, Daniel C. Buehler, Valerie A. Kickhoefer, Michael E. Rome, Leonard H. Rome, and Paul A. Wender . Vault Nanoparticles: Chemical Modifications for Imaging and Enhanced Delivery. ACS Nano 2017, 11 (1) , 872-881. DOI: 10.1021/acsnano.6b07440.
He Tian, Alexandre Fürstenberg, and Thomas Huber . Labeling and Single-Molecule Methods To Monitor G Protein-Coupled Receptor Dynamics. Chemical Reviews 2017, 117 (1) , 186-245. DOI: 10.1021/acs.chemrev.6b00084.
Quan Luo, Chunxi Hou, Yushi Bai, Ruibing Wang, and Junqiu Liu . Protein Assembly: Versatile Approaches to Construct Highly Ordered Nanostructures. Chemical Reviews 2016, 116 (22) , 13571-13632. DOI: 10.1021/acs.chemrev.6b00228.
Xu-Guang Yin, Xiao-Fei Gao, Jing-Jing Du, Xiao-Kang Zhang, Xiang-Zhao Chen, Jian Wang, Ling-Ming Xin, Ze Lei, Zheng Liu, and Jun Guo . Preparation of Protein Conjugates via Homobifunctional Diselenoester Cross-Linker. Organic Letters 2016, 18 (22) , 5796-5799. DOI: 10.1021/acs.orglett.6b02568.
Yuan Cao, Giang K. T. Nguyen, Samuel Chuah, James P. Tam, and Chuan-Fa Liu . Butelase-Mediated Ligation as an Efficient Bioconjugation Method for the Synthesis of Peptide Dendrimers. Bioconjugate Chemistry 2016, 27 (11) , 2592-2596. DOI: 10.1021/acs.bioconjchem.6b00538.
Emma M. Pelegri-O’Day and Heather D. Maynard . Controlled Radical Polymerization as an Enabling Approach for the Next Generation of Protein–Polymer Conjugates. Accounts of Chemical Research 2016, 49 (9) , 1777-1785. DOI: 10.1021/acs.accounts.6b00258.
Jens Willwacher, Ritu Raj, Shabaz Mohammed, and Benjamin G. Davis . Selective Metal-Site-Guided Arylation of Proteins. Journal of the American Chemical Society 2016, 138 (28) , 8678-8681. DOI: 10.1021/jacs.6b04043.
Tao Zhang, Xiaoyu Niu, Tao Yuan, Marco Tessari, Marcel P. de Vries, Hjalmar P. Permentier, and Rainer Bischoff . Efficient and Selective Chemical Labeling of Electrochemically Generated Peptides Based on Spirolactone Chemistry. Analytical Chemistry 2016, 88 (12) , 6465-6471. DOI: 10.1021/acs.analchem.6b01154.
Marta I. Gutiérrez-Jiménez, Carlos Aydillo, Claudio D. Navo, Alberto Avenoza, Francisco Corzana, Gonzalo Jiménez-Osés, María M. Zurbano, Jesús H. Busto, and Jesús M. Peregrina . Bifunctional Chiral Dehydroalanines for Peptide Coupling and Stereoselective S-Michael Addition. Organic Letters 2016, 18 (12) , 2796-2799. DOI: 10.1021/acs.orglett.6b00840.
Chun Ling Tung, Clarence T. T. Wong, Eva Yi Man Fung, and Xuechen Li . Traceless and Chemoselective Amine Bioconjugation via Phthalimidine Formation in Native Protein Modification. Organic Letters 2016, 18 (11) , 2600-2603. DOI: 10.1021/acs.orglett.6b00983.
Robert M. F. van der Put, Tae Hee Kim, Catherine Guerreiro, Françoise Thouron, Peter Hoogerhout, Philippe J. Sansonetti, Janny Westdijk, Michiel Stork, Armelle Phalipon, and Laurence A. Mulard . A Synthetic Carbohydrate Conjugate Vaccine Candidate against Shigellosis: Improved Bioconjugation and Impact of Alum on Immunogenicity. Bioconjugate Chemistry 2016, 27 (4) , 883-892. DOI: 10.1021/acs.bioconjchem.5b00617.
Donald A. Tomalia , Shiv N. Khanna . A Systematic Framework and Nanoperiodic Concept for Unifying Nanoscience: Hard/Soft Nanoelements, Superatoms, Meta-Atoms, New Emerging Properties, Periodic Property Patterns, and Predictive Mendeleev-like Nanoperiodic Tables. Chemical Reviews 2016, 116 (4) , 2705-2774. DOI: 10.1021/acs.chemrev.5b00367.
Jana Herzberger, Kerstin Niederer, Hannah Pohlit, Jan Seiwert, Matthias Worm, Frederik R. Wurm, and Holger Frey . Polymerization of Ethylene Oxide, Propylene Oxide, and Other Alkylene Oxides: Synthesis, Novel Polymer Architectures, and Bioconjugation. Chemical Reviews 2016, 116 (4) , 2170-2243. DOI: 10.1021/acs.chemrev.5b00441.
Kristen A. Andersen, Thomas P. Smith, Jo E. Lomax, and Ronald T. Raines . Boronic Acid for the Traceless Delivery of Proteins into Cells. ACS Chemical Biology 2016, 11 (2) , 319-323. DOI: 10.1021/acschembio.5b00966.
Yuntao Zhou, Lijie Li, Hebo Ye, Ling Zhang, and Lei You . Quantitative Reactivity Scales for Dynamic Covalent and Systems Chemistry. Journal of the American Chemical Society 2016, 138 (1) , 381-389. DOI: 10.1021/jacs.5b11361.
Yingche Chen, Kelvin Tsao, Élise De Francesco, and Jeffrey W. Keillor . Ring Substituent Effects on the Thiol Addition and Hydrolysis Reactions of N-Arylmaleimides. The Journal of Organic Chemistry 2015, 80 (24) , 12182-12192. DOI: 10.1021/acs.joc.5b02036.
Steven B. Coffey, Gary Aspnes, and Allyn T. Londregan . Expedient Synthesis of N1-Substituted Triazole Peptidomimetics. ACS Combinatorial Science 2015, 17 (12) , 706-709. DOI: 10.1021/acscombsci.5b00150.
Judy Ventura, Scott J. Eron, Daniella C. González-Toro, Kishore Raghupathi, Feng Wang, Jeanne A. Hardy, and S. Thayumanavan . Reactive Self-Assembly of Polymers and Proteins to Reversibly Silence a Killer Protein. Biomacromolecules 2015, 16 (10) , 3161-3171. DOI: 10.1021/acs.biomac.5b00779.
Alberto Nilo, Irene Passalacqua, Monica Fabbrini, Martin Allan, Aimee Usera, Filippo Carboni, Barbara Brogioni, Alfredo Pezzicoli, Jennifer Cobb, Maria Rosaria Romano, Immaculada Margarit, Qi-Ying Hu, Francesco Berti, and Roberto Adamo . Exploring the Effect of Conjugation Site and Chemistry on the Immunogenicity of an anti-Group B Streptococcus Glycoconjugate Vaccine Based on GBS67 Pilus Protein and Type V Polysaccharide. Bioconjugate Chemistry 2015, 26 (8) , 1839-1849. DOI: 10.1021/acs.bioconjchem.5b00365.
Laura Breucker, Susanne Schöttler, Katharina Landfester, and Andreas Taden . Polyurethane Dispersions with Peptide Corona: Facile Synthesis of Stimuli-Responsive Dispersions and Films. Biomacromolecules 2015, 16 (8) , 2418-2426. DOI: 10.1021/acs.biomac.5b00672.
Adel M. ElSohly and Matthew B. Francis . Development of Oxidative Coupling Strategies for Site-Selective Protein Modification. Accounts of Chemical Research 2015, 48 (7) , 1971-1978. DOI: 10.1021/acs.accounts.5b00139.
Alberto Nilo, Laura Morelli, Irene Passalacqua, Barbara Brogioni, Martin Allan, Filippo Carboni, Alfredo Pezzicoli, Francesca Zerbini, Domenico Maione, Monica Fabbrini, Maria Rosaria Romano, Qi-Ying Hu, Immaculada Margarit, Francesco Berti, and Roberto Adamo . Anti-Group B Streptococcus Glycan-Conjugate Vaccines Using Pilus Protein GBS80 As Carrier and Antigen: Comparing Lysine and Tyrosine-directed Conjugation. ACS Chemical Biology 2015, 10 (7) , 1737-1746. DOI: 10.1021/acschembio.5b00247.
Erwan Galardon and Dominique Padovani . Reactivity of Persulfides Toward Strained Bicyclo[6.1.0]nonyne Derivatives: Relevance to Chemical Tagging of Proteins. Bioconjugate Chemistry 2015, 26 (6) , 1013-1016. DOI: 10.1021/acs.bioconjchem.5b00243.
Míriam Salvadó, Beatrice Amgarten, Sergio Castillón, Gonçalo J. L. Bernardes, and Omar Boutureira . Synthesis of Fluorosugar Reagents for the Construction of Well-Defined Fluoroglycoproteins. Organic Letters 2015, 17 (11) , 2836-2839. DOI: 10.1021/acs.orglett.5b01259.
Yingqian Zhang, Chuanlong Zang, Guoce An, Mengdi Shang, Zenghui Cui, Gong Chen, Zhen Xi, Chuanzheng Zhou. Cysteine-specific protein multi-functionalization and disulfide bridging using 3-bromo-5-methylene pyrrolones. Nature Communications 2020, 11 (1) DOI: 10.1038/s41467-020-14757-4.
Xin Li, Chao Lu, Wenquan Xia, Guilan Quan, Ying Huang, Xuequn Bai, Feiyuan Yu, Qian Xu, Wanbing Qin, Daojun Liu, Xin Pan. Poly(L-Glutamic Acid)-Based Brush Copolymers: Fabrication, Self-assembly, and Evaluation as Efficient Nanocarriers for Cationic Protein Drug Delivery. AAPS PharmSciTech 2020, 21 (3) DOI: 10.1208/s12249-020-1624-4.
Mineto Uchiyama, Masahiro Osumi, Kotaro Satoh, Masami Kamigaito. Thiol-Ene Cationic and Radical Reactions: Cyclization, Step-Growth, and Concurrent Polymerizations for Thioacetal and Thioether Units. Angewandte Chemie International Edition 2020, 68 DOI: 10.1002/anie.201915132.
Mineto Uchiyama, Masahiro Osumi, Kotaro Satoh, Masami Kamigaito. Thiol‐Ene Cationic and Radical Reactions: Cyclization, Step‐Growth, and Concurrent Polymerizations for Thioacetal and Thioether Units. Angewandte Chemie 2020, DOI: 10.1002/ange.201915132.
Youshan Li, Zhenbang Lou, Hongyun Li, Haijun Yang, Yufen Zhao, Hua Fu. Bioorthogonal Ligation and Cleavage by Reactions of Chloroquinoxalines with ortho ‐Dithiophenols. Angewandte Chemie 2020, 132 (9) , 3700-3706. DOI: 10.1002/ange.201913620.
Youshan Li, Zhenbang Lou, Hongyun Li, Haijun Yang, Yufen Zhao, Hua Fu. Bioorthogonal Ligation and Cleavage by Reactions of Chloroquinoxalines with ortho -Dithiophenols. Angewandte Chemie International Edition 2020, 59 (9) , 3671-3677. DOI: 10.1002/anie.201913620.
Shinsuke Mizumoto, Siqi Xi, Yusuke Fujiwara, Shigehiro A. Kawashima, Kenzo Yamatsugu, Motomu Kanai. Hydroxamic Acid‐Piperidine Conjugate is an Activated Catalyst for Lysine Acetylation under Physiological Conditions. Chemistry – An Asian Journal 2020, DOI: 10.1002/asia.201901737.
Kenward Vong, Tomoya Yamamoto, Katsunori Tanaka. Artificial Glycoproteins as a Scaffold for Targeted Drug Therapy. Small 2020, 258, 1906890. DOI: 10.1002/smll.201906890.
António Pereira, Sérgio Martins, Ana Teresa Caldeira. Coumarins as Fluorescent Labels of Biomolecules. 2020,, DOI: 10.5772/intechopen.85973.
Kazuyoshi Yamauchi, Yasushi Kawakami. The redox status of cysteine thiol residues of apolipoprotein E impacts on its lipid interactions. Biological Chemistry , Article ASAP.
Yusuke Yoneda, Daiji Kato, Masaharu Kondo, Kenji V. P. Nagashima, Hiroshi Miyasaka, Yutaka Nagasawa, Takehisa Dewa. Sequential energy transfer driven by monoexponential dynamics in a biohybrid light-harvesting complex 2 (LH2). Photosynthesis Research 2020, 143 (2) , 115-128. DOI: 10.1007/s11120-019-00677-y.
Marjan Chahardahcherik, Mahboobeh Ashrafi, Younes Ghasemi, Mahmoud Aminlari. Effect of chemical modification with carboxymethyl dextran on kinetic and structural properties of L-asparaginase. Analytical Biochemistry 2020, 591, 113537. DOI: 10.1016/j.ab.2019.113537.
Bibifatima Kaupbayeva, Alan J. Russell. Polymer-enhanced biomacromolecules. Progress in Polymer Science 2020, 101, 101194. DOI: 10.1016/j.progpolymsci.2019.101194.
Song Song, Xinyao Li, Jialiang Wei, Weijin Wang, Yiqun Zhang, Lingsheng Ai, Yuchao Zhu, Xiaomeng Shi, Xiaohui Zhang, Ning Jiao. DMSO-catalysed late-stage chlorination of (hetero)arenes. Nature Catalysis 2020, 3 (2) , 107-115. DOI: 10.1038/s41929-019-0398-0.
Hok-Ming Ko, Jie-Ren Deng, Jian-Fang Cui, Karen Ka-Yan Kung, Yun-Chung Leung, Man-Kin Wong. Selective modification of alkyne-linked peptides and proteins by cyclometalated gold(III) (C^N) complex-mediated alkynylation. Bioorganic & Medicinal Chemistry 2020, , 115375. DOI: 10.1016/j.bmc.2020.115375.
Qiang Peng, Berlin Zang, Wei Zhao, Da Li, Jun Ren, Fangling Ji, Lingyun Jia. Efficient continuous-flow aldehyde tag conversion using immobilized formylglycine generating enzyme. Catalysis Science & Technology 2020, 10 (2) , 484-492. DOI: 10.1039/C9CY01856E.
Ka-Chung Tong, Chun-Nam Lok, Pui-Ki Wan, Di Hu, Yi Man Eva Fung, Xiao-Yong Chang, Song Huang, Haibo Jiang, Chi-Ming Che. An anticancer gold(III)-activated porphyrin scaffold that covalently modifies protein cysteine thiols. Proceedings of the National Academy of Sciences 2020, 117 (3) , 1321-1329. DOI: 10.1073/pnas.1915202117.
Michèle Salmain, Nathalie Fischer-Durand, Bogna Rudolf. Bioorthogonal Conjugation of Transition Organometallic Complexes to Peptides and Proteins: Strategies and Applications. European Journal of Inorganic Chemistry 2020, 2020 (1) , 21-35. DOI: 10.1002/ejic.201900810.
Jason P. Holland, Melanie Gut, Simon Klingler, Rachael Fay, Amaury Guillou. Photochemical Reactions in the Synthesis of Protein–Drug Conjugates. Chemistry – A European Journal 2020, 26 (1) , 33-48. DOI: 10.1002/chem.201904059.
Rajesh Kumar, Kapil Dev Sayala, Yakun Cao, Nicolay V. Tsarevsky. Functionalization of cis‐1,4‐polyisoprene using hypervalent iodine compounds with tetrazole ligands. Journal of Polymer Science 2020, 58 (1) , 172-180. DOI: 10.1002/pola.29500.
Christina Picken, Sahar Awwad, Mire Zloh, Hanieh Khalili, Steve Brocchini. Protein modification by bis-alkylation. 2020,,, 351-385. DOI: 10.1016/B978-0-444-64081-9.00016-4.
Lujuan Xu, Marco Raabe, Maksymilian M. Zegota, João C. F. Nogueira, Vijay Chudasama, Seah Ling Kuan, Tanja Weil. Site-selective protein modification via disulfide rebridging for fast tetrazine/ trans -cyclooctene bioconjugation. Organic & Biomolecular Chemistry 2020, 10 DOI: 10.1039/C9OB02687H.
Xianfeng Liu, Lue Xiang, Jiayi Li, Ying Wu, Ke Zhang. Stoichiometric imbalance-promoted step-growth polymerization based on self-accelerating 1,3-dipolar cycloaddition click reactions. Polymer Chemistry 2020, 11 (1) , 125-134. DOI: 10.1039/C9PY01362H.
Hang Chen, Hebo Ye, Yu Hai, Ling Zhang, Lei You. n→π* Interactions as A Versatile Tool for Controlling Dynamic Imine Chemistry in Both Organic and Aqueous Media. Chemical Science 2020, DOI: 10.1039/C9SC05698J.
Gargi Roy, Jason Reier, Andrew Garcia, Tom Martin, Megan Rice, Jihong Wang, Meagan Prophet, Ronald Christie, William Dall’Acqua, Sanjeev Ahuja, Michael A Bowen, Marcello Marelli. Development of a high yielding expression platform for the introduction of non-natural amino acids in protein sequences. mAbs 2020, 12 (1) , 1684749. DOI: 10.1080/19420862.2019.1684749.
Anaïs F. M. Noisier, Magnus J. Johansson, Laurent Knerr, Martin A. Hayes, William J. Drury, Eric Valeur, Lara R. Malins, Ranganath Gopalakrishnan. Late‐Stage Functionalization of Histidine in Unprotected Peptides. Angewandte Chemie 2019, 131 (52) , 19272-19278. DOI: 10.1002/ange.201910888.
Anaïs F. M. Noisier, Magnus J. Johansson, Laurent Knerr, Martin A. Hayes, William J. Drury, Eric Valeur, Lara R. Malins, Ranganath Gopalakrishnan. Late-Stage Functionalization of Histidine in Unprotected Peptides. Angewandte Chemie International Edition 2019, 58 (52) , 19096-19102. DOI: 10.1002/anie.201910888.
Lisandra Herrera Belén, Carlota de Oliveira Rangel-Yagui, Jorge F. Beltrán Lissabet, Brian Effer, Manuel Lee-Estevez, Adalberto Pessoa, Rodrigo L. Castillo, Jorge G. Farías. From Synthesis to Characterization of Site-Selective PEGylated Proteins. Frontiers in Pharmacology 2019, 10 DOI: 10.3389/fphar.2019.01450.
Bo Ding, Yue Weng, Yunqing Liu, Chunlan Song, Le Yin, Jiafan Yuan, Yanrui Ren, Aiwen Lei, Chien-Wei Chiang. Selective Photoredox Trifluoromethylation of Tryptophan-Containing Peptides. European Journal of Organic Chemistry 2019, 2019 (46) , 7596-7605. DOI: 10.1002/ejoc.201901572.
Arnaud Peramo, Anaëlle Dumas, Hynd Remita, Mireille Benoît, Stephanie Yen-Nicolay, Raphaël Corre, Ruy A. Louzada, Corinne Dupuy, Shannon Pecnard, Benoit Lambert, Jacques Young, Didier Desmaële, Patrick Couvreur. Selective modification of a native protein in a patient tissue homogenate using palladium nanoparticles. Chemical Communications 2019, 55 (100) , 15121-15124. DOI: 10.1039/C9CC07803G.
Calise Bahou, Richard J. Spears, Abil E. Aliev, Antoine Maruani, Marcos Fernandez, Faiza Javaid, Peter A. Szijj, James R. Baker, Vijay Chudasama. Use of pyridazinediones as extracellular cleavable linkers through reversible cysteine conjugation. Chemical Communications 2019, 55 (98) , 14829-14832. DOI: 10.1039/C9CC08362F.
Iveta Klimánková, Martin Hubálek, Václav Matoušek, Petr Beier. Synthesis of water-soluble hypervalent iodine reagents for fluoroalkylation of biological thiols. Organic & Biomolecular Chemistry 2019, 17 (47) , 10097-10102. DOI: 10.1039/C9OB02115A.
Takuya Matsumoto, Ryosuke Yamada, Hiroyasu Ogino. Chemical treatments for modification and immobilization to improve the solvent-stability of lipase. World Journal of Microbiology and Biotechnology 2019, 35 (12) DOI: 10.1007/s11274-019-2777-8.
Xiaobing Wang, Xiuzhen Chen, Junren Li, Xuanxuan Zhou, Yanting Liu, Liting Zhong, Yun Tang, Hai Zheng, Jiyun Liu, Ruoting Zhan, Likai Chen. Global analysis of lysine succinylation in patchouli plant leaves. Horticulture Research 2019, 6 (1) DOI: 10.1038/s41438-019-0216-5.
Qunfeng Luo, Youqi Tao, Wangjian Sheng, Jingxia Lu, Huan Wang. Dinitroimidazoles as bifunctional bioconjugation reagents for protein functionalization and peptide macrocyclization. Nature Communications 2019, 10 (1) DOI: 10.1038/s41467-018-08010-2.
Tomohisa Sawada, Yuuki Inomata, Koya Shimokawa, Makoto Fujita. A metal–peptide capsule by multiple ring threading. Nature Communications 2019, 10 (1) DOI: 10.1038/s41467-019-13594-4.
Marialuisa Siepi, Giuliana Donadio, Principia Dardano, Luca De Stefano, Daria Maria Monti, Eugenio Notomista. Denatured lysozyme-coated carbon nanotubes: a versatile biohybrid material. Scientific Reports 2019, 9 (1) DOI: 10.1038/s41598-019-52701-9.
Jie-Ren Deng, Sai-Fung Chung, Alan Siu-Lun Leung, Wai-Ming Yip, Bin Yang, Man-Chung Choi, Jian-Fang Cui, Karen Ka-Yan Kung, Zhen Zhang, Kar-Wai Lo, Yun-Chung Leung, Man-Kin Wong. Chemoselective and photocleavable cysteine modification of peptides and proteins using isoxazoliniums. Communications Chemistry 2019, 2 (1) DOI: 10.1038/s42004-019-0193-5.
Veymar G. Tacias-Pascacio, Esmeralda García-Parra, Gilber Vela-Gutiérrez, Jose J. Virgen-Ortiz, Ángel Berenguer-Murcia, Andrés R. Alcántara, Roberto Fernandez-Lafuente. Genipin as An Emergent Tool in the Design of Biocatalysts: Mechanism of Reaction and Applications. Catalysts 2019, 9 (12) , 1035. DOI: 10.3390/catal9121035.
Yabin Meng, Shuyan Han, Zhipeng Gu, Jun Wu. Cysteine‐Based Biomaterials as Drug Nanocarriers. Advanced Therapeutics 2019, 29, 1900142. DOI: 10.1002/adtp.201900142.
Yahui Zhang, Dawei Yang, Ying Li, Xiangyu Zhao, Baomin Wang, Jingping Qu. Biomimetic catalytic oxidative coupling of thiols using thiolate-bridged dinuclear metal complexes containing iron in water under mild conditions. Catalysis Science & Technology 2019, 9 (22) , 6492-6502. DOI: 10.1039/C9CY01667H.
Katsuya Maruyama, Motomu Kanai. Synthetic Methodology-driven Chemical Protein Modifications. Chemistry Letters 2019, 48 (11) , 1421-1432. DOI: 10.1246/cl.190652.
Kei Yamada, Yuji Ito. Recent Chemical Approaches for Site‐Specific Conjugation of Native Antibodies: Technologies toward Next‐Generation Antibody–Drug Conjugates. ChemBioChem 2019, 20 (21) , 2729-2737. DOI: 10.1002/cbic.201900178.
Arif Sercan Şahutoğlu, Cahit Akgül. Fine-tuned preparation of cross-linked laccase nanoaggregates. Biocatalysis and Biotransformation 2019, 37 (6) , 431-447. DOI: 10.1080/10242422.2019.1602610.
Hoi‐Yi Sit, Bin Yang, Karen Ka‐Yan Kung, John Siu‐Lun Tam, Man‐Kin Wong. Fluorescent Labelling of Glycans with FRET‐Based Probes in a Gold(III)‐Mediated Three‐Component Coupling Reaction. ChemPlusChem 2019, 84 (11) , 1739-1743. DOI: 10.1002/cplu.201900612.
Xia Liu, Mallorie Boron, Yu Zhao, Xue-Long Sun. End-point modification of recombinant thrombomodulin with enhanced stability and anticoagulant activity. European Journal of Pharmaceutical Sciences 2019, 139, 105066. DOI: 10.1016/j.ejps.2019.105066.
Eugénie Fournier, Sybille Tachon, Nicholas J. Fowler, Guillaume Gerbaud, Pascal Mansuelle, Pierre Dorlet, Sam P. Visser, Valérie Belle, A. Jalila Simaan, Marlène Martinho. The Hunt for the Closed Conformation of the Fruit‐Ripening Enzyme 1‐Aminocyclopropane‐1‐carboxylic Oxidase: A Combined Electron Paramagnetic Resonance and Molecular Dynamics Study. Chemistry – A European Journal 2019, 25 (60) , 13766-13776. DOI: 10.1002/chem.201903003.
Qing Shao. A computational avenue towards understanding and design of zwitterionic anti-biofouling materials. Molecular Simulation 2019, 45 (14-15) , 1211-1222. DOI: 10.1080/08927022.2019.1599118.
Ghazal Farahavar, Samira Sadat Abolmaali, Nasser Gholijani, Foroogh Nejatollahi. Antibody-guided nanomedicines as novel breakthrough therapeutic, diagnostic and theranostic tools. Biomaterials Science 2019, 7 (10) , 4000-4016. DOI: 10.1039/C9BM00931K.
Saumitra Sengupta, Srinivasan Chandrasekaran. Modifications of amino acids using arenediazonium salts. Organic & Biomolecular Chemistry 2019, 17 (36) , 8308-8329. DOI: 10.1039/C9OB01471C.
Sybille Tachon, Eugénie Fournier, Christophe Decroos, Pascal Mansuelle, Emilien Etienne, Marc Maresca, Marlène Martinho, Valérie Belle, Thierry Tron, Ariane Jalila Simaan. Chemical Modification of 1-Aminocyclopropane Carboxylic Acid (ACC) Oxidase: Cysteine Mutational Analysis, Characterization, and Bioconjugation with a Nitroxide Spin Label. Molecular Biotechnology 2019, 61 (9) , 650-662. DOI: 10.1007/s12033-019-00191-5.
Rafael C. Rodrigues, Jose J. Virgen-Ortíz, José C.S. dos Santos, Ángel Berenguer-Murcia, Andres R. Alcantara, Oveimar Barbosa, Claudia Ortiz, Roberto Fernandez-Lafuente. Immobilization of lipases on hydrophobic supports: immobilization mechanism, advantages, problems, and solutions. Biotechnology Advances 2019, 37 (5) , 746-770. DOI: 10.1016/j.biotechadv.2019.04.003.
Chunlan Song, Kun Liu, Zhongjie Wang, Bo Ding, Shengchun Wang, Yue Weng, Chien-Wei Chiang, Aiwen Lei. Electrochemical oxidation induced selective tyrosine bioconjugation for the modification of biomolecules. Chemical Science 2019, 10 (34) , 7982-7987. DOI: 10.1039/C9SC02218J.
Qing Zhang, Lin Li, Qiuyu Lan, Meili Li, Dingtao Wu, Hong Chen, Yaowen Liu, Derong Lin, Wen Qin, Zhiqing Zhang, Jiang Liu, Wenyu Yang. Protein glycosylation: a promising way to modify the functional properties and extend the application in food system. Critical Reviews in Food Science and Nutrition 2019, 59 (15) , 2506-2533. DOI: 10.1080/10408398.2018.1507995.
Tobias Brandhofer, Olga García Mancheño. Versatile Ru‐Photoredox‐Catalyzed Functionalization of Dehydro‐Amino Acids and Peptides. ChemCatChem 2019, 11 (16) , 3797-3801. DOI: 10.1002/cctc.201900446.
Naomi S. Robertson, Stephen J. Walsh, Elaine Fowler, Masao Yoshida, Sam M. Rowe, Yuteng Wu, Hannah F. Sore, Jeremy S. Parker, David R. Spring. Macrocyclisation and functionalisation of unprotected peptides via divinyltriazine cysteine stapling. Chemical Communications 2019, 55 (64) , 9499-9502. DOI: 10.1039/C9CC05042F.
Romain Tessier, Javier Ceballos, Nora Guidotti, Raphael Simonet-Davin, Beat Fierz, Jerome Waser. “Doubly Orthogonal” Labeling of Peptides and Proteins. Chem 2019, 5 (8) , 2243-2263. DOI: 10.1016/j.chempr.2019.06.022.
Robert E. Thompson, Adam J. Stevens, Tom. W. Muir. Protein engineering through tandem transamidation. Nature Chemistry 2019, 11 (8) , 737-743. DOI: 10.1038/s41557-019-0281-2.
Kaiye Wang, Yanan Xiang, Zhujun Shi, Hongyu Wang, Na Li, Bo Tang. Asymmetric kinetic resolution of sulfides for the construction of unsymmetric sulfides and chiral 3,3-disubstituted oxindoles. Organic & Biomolecular Chemistry 2019, 17 (26) , 6351-6354. DOI: 10.1039/C9OB01065C.
El-Hocine Siar, Roberto Morellon-Sterling, Mohammed Nasreddine Zidoune, Roberto Fernandez-Lafuente. Amination of ficin extract to improve its immobilization on glyoxyl-agarose: Improved stability and activity versus casein. International Journal of Biological Macromolecules 2019, 133, 412-419. DOI: 10.1016/j.ijbiomac.2019.04.123.
Hojat Veisi, Taibeh Tamoradi, Bikash Karmakar. An efficient clean methodology for the C–S coupling to aryl thioethers and S–S homocoupling to aromatic disulfides catalyzed over a Ce( iv )-leucine complex immobilized on mesoporous MCM-41. New Journal of Chemistry 2019, 43 (26) , 10343-10351. DOI: 10.1039/C9NJ02270H.
Marion Garreau, Franck Le Vaillant, Jerome Waser. C‐Terminal Bioconjugation of Peptides through Photoredox Catalyzed Decarboxylative Alkynylation. Angewandte Chemie 2019, 131 (24) , 8266-8270. DOI: 10.1002/ange.201901922.
Marion Garreau, Franck Le Vaillant, Jerome Waser. C-Terminal Bioconjugation of Peptides through Photoredox Catalyzed Decarboxylative Alkynylation. Angewandte Chemie International Edition 2019, 58 (24) , 8182-8186. DOI: 10.1002/anie.201901922.
Mari Takahara, Rie Wakabayashi, Naoki Fujimoto, Kosuke Minamihata, Masahiro Goto, Noriho Kamiya. Enzymatic Cell‐Surface Decoration with Proteins using Amphiphilic Lipid‐Fused Peptide Substrates. Chemistry – A European Journal 2019, 25 (30) , 7315-7321. DOI: 10.1002/chem.201900370.
Guang Yang, Yue Lu, Hunter N. Bomba, Zhen Gu. Cysteine-rich Proteins for Drug Delivery and Diagnosis. Current Medicinal Chemistry 2019, 26 (8) , 1377-1388. DOI: 10.2174/0929867324666170920163156.
Carlos Aydillo, Nuria Mazo, Claudio D. Navo, Gonzalo Jiménez‐Osés. Elusive Dehydroalanine Derivatives with Enhanced Reactivity. ChemBioChem 2019, 20 (10) , 1246-1250. DOI: 10.1002/cbic.201800758.
Maria J. Matos, Claudio D. Navo, Tuuli Hakala, Xhenti Ferhati, Ana Guerreiro, David Hartmann, Barbara Bernardim, Kadi L. Saar, Ismael Compañón, Francisco Corzana, Tuomas P. J. Knowles, Gonzalo Jiménez‐Osés, Gonçalo J. L. Bernardes. Quaternization of Vinyl/Alkynyl Pyridine Enables Ultrafast Cysteine‐Selective Protein Modification and Charge Modulation. Angewandte Chemie 2019, 131 (20) , 6712-6716. DOI: 10.1002/ange.201901405.
Maria J. Matos, Claudio D. Navo, Tuuli Hakala, Xhenti Ferhati, Ana Guerreiro, David Hartmann, Barbara Bernardim, Kadi L. Saar, Ismael Compañón, Francisco Corzana, Tuomas P. J. Knowles, Gonzalo Jiménez-Osés, Gonçalo J. L. Bernardes. Quaternization of Vinyl/Alkynyl Pyridine Enables Ultrafast Cysteine-Selective Protein Modification and Charge Modulation. Angewandte Chemie International Edition 2019, 58 (20) , 6640-6644. DOI: 10.1002/anie.201901405.
Julia Ertl, Maria Elena Ortiz‐Soto, Thien Anh Le, Julian Bechold, Junwen Shan, Jörg Teßmar, Bernd Engels, Jürgen Seibel. Tuning the Product Spectrum of a Glycoside Hydrolase Enzyme by a Combination of Site‐Directed Mutagenesis and Tyrosine‐Specific Chemical Modification. Chemistry – A European Journal 2019, 25 (26) , 6533-6541. DOI: 10.1002/chem.201900576.
Jun Ohata, Samuel C. Martin, Zachary T. Ball. Metallvermittelte Funktionalisierung natürlicher Peptide und Proteine: Biokonjugation mit Übergangsmetallen. Angewandte Chemie 2019, 131 (19) , 6238-6264. DOI: 10.1002/ange.201807536.
Jun Ohata, Samuel C. Martin, Zachary T. Ball. Metal-Mediated Functionalization of Natural Peptides and Proteins: Panning for Bioconjugation Gold. Angewandte Chemie International Edition 2019, 58 (19) , 6176-6199. DOI: 10.1002/anie.201807536.
Alessandro Ruffoni, Fabio Juliá, Thomas D. Svejstrup, Alastair J. McMillan, James J. Douglas, Daniele Leonori. Practical and regioselective amination of arenes using alkyl amines. Nature Chemistry 2019, 11 (5) , 426-433. DOI: 10.1038/s41557-019-0254-5.
Kei Yamada, Natsuki Shikida, Kazutaka Shimbo, Yuji Ito, Zahra Khedri, Yutaka Matsuda, Brian A. Mendelsohn. AJICAP: Affinity Peptide Mediated Regiodivergent Functionalization of Native Antibodies. Angewandte Chemie 2019, 131 (17) , 5648-5653. DOI: 10.1002/ange.201814215.
Kei Yamada, Natsuki Shikida, Kazutaka Shimbo, Yuji Ito, Zahra Khedri, Yutaka Matsuda, Brian A. Mendelsohn. AJICAP: Affinity Peptide Mediated Regiodivergent Functionalization of Native Antibodies. Angewandte Chemie International Edition 2019, 58 (17) , 5592-5597. DOI: 10.1002/anie.201814215.
Vladimir A. Larionov, Nadezhda V. Stoletova, Vladislav I. Kovalev, Alexander F. Smol'yakov, Tat'yana F. Savel'yeva, Victor I. Maleev. A general synthesis of unnatural α-amino acids by iron-catalysed olefin–olefin coupling via generated radicals. Organic Chemistry Frontiers 2019, 6 (8) , 1094-1099. DOI: 10.1039/C9QO00108E.
Felix Tobola, Elise Sylvander, Claudia Gafko, Birgit Wiltschi. ‘Clickable lectins’: bioorthogonal reactive handles facilitate the directed conjugation of lectins in a modular fashion. Interface Focus 2019, 9 (2) , 20180072. DOI: 10.1098/rsfs.2018.0072.
Chi Zhang, Ekaterina V. Vinogradova, Alexander M. Spokoyny, Stephen L. Buchwald, Bradley L. Pentelute. Arylierungschemie für die Biokonjugation. Angewandte Chemie 2019, 131 (15) , 4860-4892. DOI: 10.1002/ange.201806009.
Chi Zhang, Ekaterina V. Vinogradova, Alexander M. Spokoyny, Stephen L. Buchwald, Bradley L. Pentelute. Arylation Chemistry for Bioconjugation. Angewandte Chemie International Edition 2019, 58 (15) , 4810-4839. DOI: 10.1002/anie.201806009.
Nathalie Fischer-Durand, Daria Lizinska, Vincent Guérineau, Bogna Rudolf, Michèle Salmain. ‘Clickable’ cyclopentadienyl iron carbonyl complexes for bioorthogonal conjugation of mid-infrared labels to a model protein and PAMAM dendrimer. Applied Organometallic Chemistry 2019, 33 (4) , e4798. DOI: 10.1002/aoc.4798.
Glen Liszczak, Tom W. Muir. Barcoding mit Nukleinsäuren: Anwendung der DNA‐Sequenzierung als molekulares Zählwerk. Angewandte Chemie 2019, 131 (13) , 4188-4207. DOI: 10.1002/ange.201808956.
Glen Liszczak, Tom W. Muir. Nucleic Acid-Barcoding Technologies: Converting DNA Sequencing into a Broad-Spectrum Molecular Counter. Angewandte Chemie International Edition 2019, 58 (13) , 4144-4162. DOI: 10.1002/anie.201808956.
Chunyang Bao, Qiang Zhang. Modulation of protein activity and assembled structure by polymer conjugation: PEGylation vs glycosylation. European Polymer Journal 2019, 112, 263-272. DOI: 10.1016/j.eurpolymj.2019.01.020.
Emily A. Hoyt, Pedro M. S. D. Cal, Bruno L. Oliveira, Gonçalo J. L. Bernardes. Contemporary approaches to site-selective protein modification. Nature Reviews Chemistry 2019, 3 (3) , 147-171. DOI: 10.1038/s41570-019-0079-1.
Kengo Hanaya, Jun Ohata, Mary K. Miller, Alicia E. Mangubat-Medina, Michael J. Swierczynski, David C. Yang, Reece M. Rosenthal, Brian V. Popp, Zachary T. Ball. Rapid nickel( ii )-promoted cysteine S -arylation with arylboronic acids. Chemical Communications 2019, 55 (19) , 2841-2844. DOI: 10.1039/C9CC00159J.
Katsunori Tanaka. Glycan Molecular Technology for Highly Selective In Vivo Recognition. 2019,,, 131-163. DOI: 10.1002/9783527823987.vol2_c7.
François-Xavier Felpin, Saumitra Sengupta. Biaryl synthesis with arenediazonium salts: cross-coupling, CH-arylation and annulation reactions. Chemical Society Reviews 2019, 48 (4) , 1150-1193. DOI: 10.1039/C8CS00453F.
Rika Sakai, Hiroki Iguchi, Tatsuo Maruyama. Quantification of azide groups on a material surface and a biomolecule using a clickable and cleavable fluorescent compound. RSC Advances 2019, 9 (8) , 4621-4625. DOI: 10.1039/C8RA09421G.
Lei Liu. Chemical Synthesis of Proteins that cannot be Obtained Recombinantly. Israel Journal of Chemistry 2019, 59 (1-2) , 64-70. DOI: 10.1002/ijch.201800135.
Daniela Barros, Paula Parreira, Joana Furtado, Frederico Ferreira-da-Silva, Eduardo Conde-Sousa, Andrés J. García, M. Cristina L. Martins, Isabel Freitas Amaral, Ana Paula Pêgo. An affinity-based approach to engineer laminin-presenting cell instructive microenvironments. Biomaterials 2019, 192, 601-611. DOI: 10.1016/j.biomaterials.2018.10.039.
Fernanda Cristina Fraga, Alexsandra Valério, Vanessa Almeida de Oliveira, Marco Di Luccio, Débora de Oliveira. Effect of magnetic field on the Eversa® Transform 2.0 enzyme: Enzymatic activity and structural conformation. International Journal of Biological Macromolecules 2019, 122, 653-658. DOI: 10.1016/j.ijbiomac.2018.10.171.
Dejun Ma, Xueying Kang, Yasi Gao, Jiqin Zhu, Long Yi, Zhen Xi. Design and synthesis of a highly efficient labelling reagent for incorporation of tetrafluorinated aromatic azide into proteins. Tetrahedron 2019, 75 (7) , 888-893. DOI: 10.1016/j.tet.2019.01.002.
Hidetoshi Teramoto, Masatoshi Iga, Hiromi Tsuboi, Kenichi Nakajima. Characterization and Scaled-Up Production of Azido-Functionalized Silk Fiber Produced by Transgenic Silkworms with an Expanded Genetic Code. International Journal of Molecular Sciences 2019, 20 (3) , 616. DOI: 10.3390/ijms20030616.
Song-Lin Zhang, Jia-Jia Dong. Mechanism and chemoselectivity origins of bioconjugation of cysteine with Au( iii )-aryl reagents. Organic & Biomolecular Chemistry 2019, 17 (5) , 1245-1253. DOI: 10.1039/C8OB03143F.
Sheng Xie, Juan Zhou, Xuan Chen, Na Kong, Yanmiao Fan, Yang Zhang, Gerry Hammer, David G. Castner, Olof Ramström, Mingdi Yan. A versatile catalyst-free perfluoroaryl azide–aldehyde–amine conjugation reaction. Materials Chemistry Frontiers 2019, 3 (2) , 251-256. DOI: 10.1039/C8QM00516H.
Jinhua Yang, Changliu Wang, Silin Xu, Junfeng Zhao. Ynamide-Mediated Thiopeptide Synthesis. Angewandte Chemie 2019, 131 (5) , 1396-1400. DOI: 10.1002/ange.201811586.
Jinhua Yang, Changliu Wang, Silin Xu, Junfeng Zhao. Ynamide-Mediated Thiopeptide Synthesis. Angewandte Chemie International Edition 2019, 58 (5) , 1382-1386. DOI: 10.1002/anie.201811586.
Seiji SAKAMOTO, Itaru HAMACHI. Recent Progress in Chemical Modification of Proteins. Analytical Sciences 2019, 35 (1) , 5-27. DOI: 10.2116/analsci.18R003.
Ruben V. Maaskant, Gerard Roelfes. Bioorthogonal Metalloporphyrin‐Catalyzed Selective Methionine Alkylation in the Lanthipeptide Nisin. ChemBioChem 2019, 20 (1) , 57-61. DOI: 10.1002/cbic.201800493.
Cecilia Bottecchia, Timothy Noël. Photocatalytic Modification of Amino Acids, Peptides, and Proteins. Chemistry – A European Journal 2019, 25 (1) , 26-42. DOI: 10.1002/chem.201803074.
João M. J. M. Ravasco, Hélio Faustino, Alexandre Trindade, Pedro M. P. Gois. Bioconjugation with Maleimides: A Useful Tool for Chemical Biology. Chemistry – A European Journal 2019, 25 (1) , 43-59. DOI: 10.1002/chem.201803174.
Kévin Renault, Clément Guillou, Pierre-Yves Renard, Cyrille Sabot. Investigation of tetrazine reactivity towards C-nucleophiles: pyrazolone-based modification of biomolecules. Organic & Biomolecular Chemistry 2019, 17 (2) , 388-396. DOI: 10.1039/C8OB02108B.
Karolina Peciak, Emmanuelle Laurine, Rita Tommasi, Ji-won Choi, Steve Brocchini. Site-selective protein conjugation at histidine. Chemical Science 2019, 10 (2) , 427-439. DOI: 10.1039/C8SC03355B.
Maria J. Matos, Gonzalo Jiménez-Osés, Gonçalo J. L. Bernardes. Lysine Bioconjugation on Native Albumin with a Sulfonyl Acrylate Reagent. 2019,,, 25-37. DOI: 10.1007/978-1-4939-9654-4_3.
Alexander Böker. Biopolymere – Funktionsträger in der Materialforschung. 2019,,, 133-163. DOI: 10.1007/978-3-662-58243-5_8.
Xiang Sheng, Qianqian Hou, Yongjun Liu. Computational evidence for the importance of lysine carboxylation in the reaction catalyzed by carboxyl transferase domain of pyruvate carboxylase: a QM/MM study. Theoretical Chemistry Accounts 2019, 138 (1) DOI: 10.1007/s00214-018-2408-8.
María Cruz-Alonso, Ana Lores-Padín, Eva Valencia, Héctor González-Iglesias, Beatriz Fernández, Rosario Pereiro. Quantitative mapping of specific proteins in biological tissues by laser ablation–ICP-MS using exogenous labels: aspects to be considered. Analytical and Bioanalytical Chemistry 2019, 411 (3) , 549-558. DOI: 10.1007/s00216-018-1411-1.
Kenward Vong, Katsunori Tanaka. Influence of Glycosylation Pattern on Protein Biodistribution and Kinetics In Vivo Within Mice. 2019,,, 127-161. DOI: 10.1016/B978-0-12-812126-9.00007-9.
Eiji Nakata, Shun Nakano, Arivazhagan Rajendran, Takashi Morii. Covalent Bond Formation by Modular Adaptors to Locate Multiple Enzymes on a DNA Scaffold. 2019,,, 163-183. DOI: 10.1016/B978-0-12-812126-9.00008-0.
Joseph C. Genereux. Mass spectrometric approaches for profiling protein folding and stability. 2019,,, 111-144. DOI: 10.1016/bs.apcsb.2019.09.006.
Daniel K. Weber, Taysir Bader, Erik K. Larsen, Songlin Wang, Tata Gopinath, Mark Distefano, Gianluigi Veglia. Cysteine-ethylation of tissue-extracted membrane proteins as a tool to detect conformational states by solid-state NMR spectroscopy. 2019,,, 281-304. DOI: 10.1016/bs.mie.2019.02.001.
Barbara Bernardim, Maria J. Matos, Xhenti Ferhati, Ismael Compañón, Ana Guerreiro, Padma Akkapeddi, Antonio C. B. Burtoloso, Gonzalo Jiménez-Osés, Francisco Corzana, Gonçalo J. L. Bernardes. Efficient and irreversible antibody–cysteine bioconjugation using carbonylacrylic reagents. Nature Protocols 2019, 14 (1) , 86-99. DOI: 10.1038/s41596-018-0083-9.
Jeong Hoon Ko, Heather D. Maynard. A guide to maximizing the therapeutic potential of protein–polymer conjugates by rational design. Chemical Society Reviews 2018, 47 (24) , 8998-9014. DOI: 10.1039/C8CS00606G.
Patrick J. Almhjell, Christina E. Boville, Frances H. Arnold. Engineering enzymes for noncanonical amino acid synthesis. Chemical Society Reviews 2018, 47 (24) , 8980-8997. DOI: 10.1039/C8CS00665B.
Tobias Brandhofer, Olga García Mancheño. Site-Selective C-H Bond Activation/Functionalization of Alpha-Amino Acids and Peptide-Like Derivatives. European Journal of Organic Chemistry 2018, 2018 (44) , 6050-6067. DOI: 10.1002/ejoc.201800896.
Luman Liu, Jared A. Shadish, Christopher K. Arakawa, Kevin Shi, Jennifer Davis, Cole A. DeForest. Cyclic Stiffness Modulation of Cell‐Laden Protein–Polymer Hydrogels in Response to User‐Specified Stimuli Including Light. Advanced Biosystems 2018, 2 (12) , 1800240. DOI: 10.1002/adbi.201800240.
Mauricio Morais, Michelle T. Ma. Site-specific chelator-antibody conjugation for PET and SPECT imaging with radiometals. Drug Discovery Today: Technologies 2018, 30, 91-104. DOI: 10.1016/j.ddtec.2018.10.002.
Diana Diana, Wangsa Tirta Ismaya, Vincencius Felix Meidianto, Olivia Mayasari Tandrasasmita, Raymond Rubianto Tjandrawinata, Heni Rachmawati. Bioconjugation of Captopril–Light Subunit of Agaricus bisporus Mushroom Tyrosinase: Characterization and Potential Use as a Drug Carrier for Oral Delivery. Biological and Pharmaceutical Bulletin 2018, 41 (12) , 1837-1842. DOI: 10.1248/bpb.b18-00553.
Wan-Min Cheng, Xi Lu, Jing Shi, Lei Liu. Selective modification of natural nucleophilic residues in peptides and proteins using arylpalladium complexes. Organic Chemistry Frontiers 2018, 5 (21) , 3186-3193. DOI: 10.1039/C8QO00765A.
Sebastian J. Siegl, Milan Vrabel. Probing the Scope of the Amidine-1,2,3-triazine Cycloaddition as a Prospective Click Ligation Method. European Journal of Organic Chemistry 2018, 2018 (37) , 5081-5085. DOI: 10.1002/ejoc.201800530.
Jiamei Yang, Lifen Sun, Renling Guo, Haiyan Yang, Xiyun Feng, Xufeng Zhang. A Facile Route for Oriented Covalent Immobilization of Recombinant Protein A on Epoxy Agarose Gels: In Situ Generation of Heterofunctional Amino-Epoxy Supports. ChemistrySelect 2018, 3 (37) , 10320-10324. DOI: 10.1002/slct.201802256.
Burcin Akgun, Dennis G. Hall. Boronsäuren als bioorthogonale Sonden für zentrenselektives Protein‐Labeling. Angewandte Chemie 2018, 130 (40) , 13210-13228. DOI: 10.1002/ange.201712611.
Burcin Akgun, Dennis G. Hall. Boronic Acids as Bioorthogonal Probes for Site-Selective Labeling of Proteins. Angewandte Chemie International Edition 2018, 57 (40) , 13028-13044. DOI: 10.1002/anie.201712611.
Lara R Malins. Peptide modification and cyclization via transition-metal catalysis. Current Opinion in Chemical Biology 2018, 46, 25-32. DOI: 10.1016/j.cbpa.2018.03.019.
Jitka Dadová, Sébastien RG Galan, Benjamin G Davis. Synthesis of modified proteins via functionalization of dehydroalanine. Current Opinion in Chemical Biology 2018, 46, 71-81. DOI: 10.1016/j.cbpa.2018.05.022.
Jiandong Cui, Baoting Sun, Tao Lin, Yuxiao Feng, Shiru Jia. Enzyme shielding by mesoporous organosilica shell on [email protected] yolk-shell nanospheres. International Journal of Biological Macromolecules 2018, 117, 673-682. DOI: 10.1016/j.ijbiomac.2018.05.227.
Sara P. Morcillo, Elizabeth M. Dauncey, Ji Hye Kim, James J. Douglas, Nadeem S. Sheikh, Daniele Leonori. Photoinduced Remote Functionalization of Amides and Amines Using Electrophilic Nitrogen Radicals. Angewandte Chemie 2018, 130 (39) , 13127-13131. DOI: 10.1002/ange.201807941.
Sara P. Morcillo, Elizabeth M. Dauncey, Ji Hye Kim, James J. Douglas, Nadeem S. Sheikh, Daniele Leonori. Photoinduced Remote Functionalization of Amides and Amines Using Electrophilic Nitrogen Radicals. Angewandte Chemie International Edition 2018, 57 (39) , 12945-12949. DOI: 10.1002/anie.201807941.
Jian Yu, Xiaoyue Yang, Yang Sun, Zheng Yin. Highly Reactive and Tracelessly Cleavable Cysteine-Specific Modification of Proteins via 4-Substituted Cyclopentenone. Angewandte Chemie 2018, 130 (36) , 11772-11776. DOI: 10.1002/ange.201804801.
Jian Yu, Xiaoyue Yang, Yang Sun, Zheng Yin. Highly Reactive and Tracelessly Cleavable Cysteine-Specific Modification of Proteins via 4-Substituted Cyclopentenone. Angewandte Chemie International Edition 2018, 57 (36) , 11598-11602. DOI: 10.1002/anie.201804801.
Zhong-Kai Zhao, Tai-Hua Mu, Miao Zhang, Aurore Richel. Chemical Forces, Structure, and Gelation Properties of Sweet Potato Protein as Affected by pH and High Hydrostatic Pressure. Food and Bioprocess Technology 2018, 11 (9) , 1719-1732. DOI: 10.1007/s11947-018-2137-y.
Xinyu Liu, Jiawei Sun, Weiping Gao. Site-selective protein modification with polymers for advanced biomedical applications. Biomaterials 2018, 178, 413-434. DOI: 10.1016/j.biomaterials.2018.04.050.
Coline Canovas, Mathieu Moreau, Claire Bernhard, Alexandra Oudot, Mélanie Guillemin, Franck Denat, Victor Goncalves. Site‐Specific Dual Labeling of Proteins on Cysteine Residues with Chlorotetrazines. Angewandte Chemie 2018, 130 (33) , 10806-10810. DOI: 10.1002/ange.201806053.
Coline Canovas, Mathieu Moreau, Claire Bernhard, Alexandra Oudot, Mélanie Guillemin, Franck Denat, Victor Goncalves. Site-Specific Dual Labeling of Proteins on Cysteine Residues with Chlorotetrazines. Angewandte Chemie International Edition 2018, 57 (33) , 10646-10650. DOI: 10.1002/anie.201806053.
Jiří Václavík, Iveta Klimánková, Alena Budinská, Petr Beier. Advances in the Synthesis and Application of Tetrafluoroethylene- and 1,1,2,2-Tetrafluoroethyl-Containing Compounds. European Journal of Organic Chemistry 2018, 2018 (27-28) , 3554-3593. DOI: 10.1002/ejoc.201701590.
Partha Sarathi Addy, James S. Italia, Abhishek Chatterjee. An Oxidative Bioconjugation Strategy Targeted to a Genetically Encoded 5-Hydroxytryptophan. ChemBioChem 2018, 19 (13) , 1375-1378. DOI: 10.1002/cbic.201800111.
De-zhi Li, Bing-nan Han, Rui Wei, Gui-yang Yao, Zhizhen Chen, Jie Liu, Terence C.W. Poon, Wu Su, Zhongyu Zhu, Dimiter S. Dimitrov, Qi Zhao. N-terminal α-amino group modification of antibodies using a site-selective click chemistry method. mAbs 2018, 10 (5) , 712-719. DOI: 10.1080/19420862.2018.1463122.
Ahmed M. Embaby, Sanne Schoffelen, Christian Kofoed, Morten Meldal, Frederik Diness. Rational Tuning of Fluorobenzene Probes for Cysteine‐Selective Protein Modification. Angewandte Chemie 2018, 130 (27) , 8154-8158. DOI: 10.1002/ange.201712589.
Ahmed M. Embaby, Sanne Schoffelen, Christian Kofoed, Morten Meldal, Frederik Diness. Rational Tuning of Fluorobenzene Probes for Cysteine-Selective Protein Modification. Angewandte Chemie International Edition 2018, 57 (27) , 8022-8026. DOI: 10.1002/anie.201712589.
Bernadette Lee, Shuang Sun, Ester Jiménez-Moreno, André A. Neves, Gonçalo J.L. Bernardes. Site-selective installation of an electrophilic handle on proteins for bioconjugation. Bioorganic & Medicinal Chemistry 2018, 26 (11) , 3060-3064. DOI: 10.1016/j.bmc.2018.02.028.
Tong Zhu, Lu Song, Ruifeng Li, Bian Wu. Enzymatic clickable functionalization of peptides via computationally engineered peptide amidase. Chinese Chemical Letters 2018, 29 (7) , 1116-1118. DOI: 10.1016/j.cclet.2018.03.033.
Shaomin Lin, Chunmao He. A mini-review on the enzyme-mediated manipulation of proteins/peptides. Chinese Chemical Letters 2018, 29 (7) , 1017-1021. DOI: 10.1016/j.cclet.2018.05.006.
Xi Lu, Shi-Jiang He, Wan-Min Cheng, Jing Shi. Transition-metal-catalyzed C H functionalization for late-stage modification of peptides and proteins. Chinese Chemical Letters 2018, 29 (7) , 1001-1008. DOI: 10.1016/j.cclet.2018.05.011.
Qi Cao, Naipu He, Yue Wang, Zhenwu Lu. Self-assembled nanostructures from amphiphilic globular protein–polymer hybrids. Polymer Bulletin 2018, 75 (6) , 2627-2639. DOI: 10.1007/s00289-017-2176-y.
Tyler J. Wadzinski, Angela Steinauer, Liana Hie, Guillaume Pelletier, Alanna Schepartz, Scott J. Miller. Rapid phenolic O-glycosylation of small molecules and complex unprotected peptides in aqueous solvent. Nature Chemistry 2018, 10 (6) , 644-652. DOI: 10.1038/s41557-018-0041-8.
Lara R. Malins. Decarboxylative couplings as versatile tools for late-stage peptide modifications. Peptide Science 2018, 110 (3) , e24049. DOI: 10.1002/pep2.24049.
Patmawati xxxx, Kosuke Minamihata, Tsuneyuki Tatsuke, Jae Man Lee, Takahiro Kusakabe, Noriho Kamiya. Expression and Activation of Horseradish Peroxidase-Protein A/G Fusion Protein in Silkworm Larvae for Diagnostic Purposes. Biotechnology Journal 2018, 14, 1700624. DOI: 10.1002/biot.201700624.
Chi-Jiun Peng, Hsiu-Ling Chen, Cheng-Hsun Chiu, Jim-Min Fang. Site-Selective Functionalization of Flagellin by Steric Self-Protection: A Strategy To Facilitate Flagellin as a Self-Adjuvanting Carrier in Conjugate Vaccine. ChemBioChem 2018, 19 (8) , 805-814. DOI: 10.1002/cbic.201700634.
Jorick J. Bruins, Bauke Albada, Floris van Delft. ortho -Quinones and Analogues Thereof: Highly Reactive Intermediates for Fast and Selective Biofunctionalization. Chemistry - A European Journal 2018, 24 (19) , 4749-4756. DOI: 10.1002/chem.201703919.
Ming Wang, Xuefeng Jiang. Sulfur–Sulfur Bond Construction. Topics in Current Chemistry 2018, 376 (2) DOI: 10.1007/s41061-018-0192-5.
Kenji Watanabe, Takashi Ohshima. Bioconjugation with Thiols by Benzylic Substitution. Chemistry - A European Journal 2018, 24 (16) , 3959-3964. DOI: 10.1002/chem.201706149.
Yanxiong Pan, Sunanda Neupane, Jasmin Farmakes, Myungkeun Oh, Kylie Bentz, Yongki Choi, Zhongyu Yang. Insights on the Structure, Molecular Weight and Activity of an Antibacterial Protein-Polymer Hybrid. ChemPhysChem 2018, 19 (5) , 651-658. DOI: 10.1002/cphc.201701097.
Rong Huang, Zhihong Li, Peiling Ren, Wenzhang Chen, Yuanyuan Kuang, Jiakang Chen, Yuexiong Zhan, Hongli Chen, Biao Jiang. N -Phenyl- N -aceto-vinylsulfonamides as Efficient and Chemoselective Handles for N-Terminal Modification of Peptides and Proteins. European Journal of Organic Chemistry 2018, 2018 (6) , 829-836. DOI: 10.1002/ejoc.201701715.
Steven Bloom, Chun Liu, Dominik K. Kölmel, Jennifer X. Qiao, Yong Zhang, Michael A. Poss, William R. Ewing, David W. C. MacMillan. Decarboxylative alkylation for site-selective bioconjugation of native proteins via oxidation potentials. Nature Chemistry 2018, 10 (2) , 205-211. DOI: 10.1038/nchem.2888.
Geisa A.L.G. Budinova, Yutaro Mori, Noriho Kamiya. Design of Artificial Supramolecular Protein Assemblies by Enzymatic Bioconjugation for Biocatalytic Reactions. 2018,,, 93-103. DOI: 10.1002/9783527803293.ch6.
Daniel B. Lookadoo, Matthew S. Beyersdorf, Christopher J. Halkides. Synthesis of a Stable Analog of the Phosphorylated Form of CheY: Phosphono-CheY. 2018,,, 337-343. DOI: 10.1007/978-1-4939-7577-8_26.
Sahar Awwad, Claire Ginn, Steve Brocchini. The case for protein PEGylation. 2018,,, 27-49. DOI: 10.1016/B978-0-08-101750-0.00002-7.
Cláudia S.M. Fernandes, Gonçalo D.G. Teixeira, Olga Iranzo, Ana C.A. Roque. Engineered Protein Variants for Bioconjugation. 2018,,, 105-138. DOI: 10.1016/B978-0-323-50878-0.00005-7.
Calise Bahou, Daniel A. Richards, Antoine Maruani, Elizabeth A. Love, Faiza Javaid, Stephen Caddick, James R. Baker, Vijay Chudasama. Highly homogeneous antibody modification through optimisation of the synthesis and conjugation of functionalised dibromopyridazinediones. Organic & Biomolecular Chemistry 2018, 16 (8) , 1359-1366. DOI: 10.1039/C7OB03138F.
Yanira Méndez, Janoi Chang, Ana R. Humpierre, Abel Zanuy, Raine Garrido, Aldrin V. Vasco, Jessy Pedroso, Darielys Santana, Laura M. Rodríguez, Dagmar García-Rivera, Yury Valdés, Vicente Vérez-Bencomo, Daniel G. Rivera. Multicomponent polysaccharide–protein bioconjugation in the development of antibacterial glycoconjugate vaccine candidates. Chemical Science 2018, 9 (9) , 2581-2588. DOI: 10.1039/C7SC05467J.
X. Shang, Y. Chen, N. Wang, W. Niu, J. Guo. Oxidation-induced generation of a mild electrophile for proximity-enhanced protein–protein crosslinking. Chemical Communications 2018, 54 (33) , 4172-4175. DOI: 10.1039/C8CC01639A.
Natalee J. Smith, Katarina Rohlfing, Lisa A. Sawicki, Prathamesh M. Kharkar, Samantha J. Boyd, April M. Kloxin, Joseph M. Fox. Fast, irreversible modification of cysteines through strain releasing conjugate additions of cyclopropenyl ketones. Organic & Biomolecular Chemistry 2018, 16 (12) , 2164-2169. DOI: 10.1039/C8OB00166A.
Anna Kovalová, Radek Pohl, Milan Vrabel. Stepwise triple-click functionalization of synthetic peptides. Organic & Biomolecular Chemistry 2018, 16 (33) , 5960-5964. DOI: 10.1039/C8OB01617H.
Naoko Ichiishi, John P. Caldwell, Melissa Lin, Wendy Zhong, Xiaohong Zhu, Eric Streckfuss, Hai-Young Kim, Craig A. Parish, Shane W. Krska. Protecting group free radical C–H trifluoromethylation of peptides. Chemical Science 2018, 9 (17) , 4168-4175. DOI: 10.1039/C8SC00368H.
Davoud Mozhdehi, Kelli M. Luginbuhl, Stefan Roberts, Ashutosh Chilkoti. Design of Sequence-Specific Polymers by Genetic Engineering. 2017,,, 91-115. DOI: 10.1002/9783527806096.ch4.
Wing Ho So, Yu Zhang, Wei Kang, Clarence T.T. Wong, Hongyan Sun, Jiang Xia. Site-selective covalent reactions on proteinogenic amino acids. Current Opinion in Biotechnology 2017, 48, 220-227. DOI: 10.1016/j.copbio.2017.06.003.
R. Christie, Arnaud Tiberghien, Qun Du, Binyam Bezabeh, Ryan Fleming, Amanda Shannon, Shenlan Mao, Shannon Breen, Jing Zhang, Haihong Zhong, Jay Harper, Herren Wu, Philip Howard, Changshou Gao. Pyrrolobenzodiazepine Antibody-Drug Conjugates Designed for Stable Thiol Conjugation. Antibodies 2017, 6 (4) , 20. DOI: 10.3390/antib6040020.
Regina Fraas, Juliane Diehm, Matthias Franzreb. Automated Solid-Phase Protein Modification with Integrated Enzymatic Digest for Reaction Validation: Application of a Compartmented Microfluidic Reactor for Rapid Optimization and Analysis of Protein Biotinylation. Frontiers in Bioengineering and Biotechnology 2017, 5 DOI: 10.3389/fbioe.2017.00072.
Cecilia Bottecchia, Maarten Rubens, Smita B. Gunnoo, Volker Hessel, Annemieke Madder, Timothy Noël. Visible-Light-Mediated Selective Arylation of Cysteine in Batch and Flow. Angewandte Chemie 2017, 129 (41) , 12876-12881. DOI: 10.1002/ange.201706700.
Cecilia Bottecchia, Maarten Rubens, Smita B. Gunnoo, Volker Hessel, Annemieke Madder, Timothy Noël. Visible-Light-Mediated Selective Arylation of Cysteine in Batch and Flow. Angewandte Chemie International Edition 2017, 56 (41) , 12702-12707. DOI: 10.1002/anie.201706700.
Jean B. Bertoldo, Tiago Rodrigues, Lavinia Dunsmore, Francesco A. Aprile, Marta C. Marques, Leonardo A. Rosado, Omar Boutureira, Thomas B. Steinbrecher, Woody Sherman, Francisco Corzana, Hernán Terenzi, Gonçalo J.L. Bernardes. A Water-Bridged Cysteine-Cysteine Redox Regulation Mechanism in Bacterial Protein Tyrosine Phosphatases. Chem 2017, 3 (4) , 665-677. DOI: 10.1016/j.chempr.2017.07.009.
Ramesh Dasari, James J. La Clair, Alexander Kornienko. Irreversible Protein Labeling by Paal-Knorr Conjugation. ChemBioChem 2017, 18 (18) , 1792-1796. DOI: 10.1002/cbic.201700210.
Panchada Ch. V. Govindu, Chidanad Sudarshan, Konkallu Hanumae Gowd. Synthesis of two closely spaced cysteine barbiturates containing peptides by copper-catalyzed oxidation of contryphan disulfide. Synthetic Communications 2017, 47 (17) , 1559-1567. DOI: 10.1080/00397911.2017.1336245.
Muhammad Jbara, Suman Kumar Maity, Ashraf Brik. Palladium in der chemischen Synthese und Modifizierung von Proteinen. Angewandte Chemie 2017, 129 (36) , 10780-10792. DOI: 10.1002/ange.201702370.
Muhammad Jbara, Suman Kumar Maity, Ashraf Brik. Palladium in the Chemical Synthesis and Modification of Proteins. Angewandte Chemie International Edition 2017, 56 (36) , 10644-10655. DOI: 10.1002/anie.201702370.
Arnaud Chevalier, Pierre-Yves Renard, Anthony Romieu. Azo-Based Fluorogenic Probes for Biosensing and Bioimaging: Recent Advances and Upcoming Challenges. Chemistry - An Asian Journal 2017, 12 (16) , 2008-2028. DOI: 10.1002/asia.201700682.
Federica Agostini, Jan‐Stefan Völler, Beate Koksch, Carlos G. Acevedo‐Rocha, Vladimir Kubyshkin, Nediljko Budisa. Biokatalyse mit nicht‐natürlichen Aminosäuren: Enzymologie trifft Xenobiologie. Angewandte Chemie 2017, 129 (33) , 9810-9835. DOI: 10.1002/ange.201610129.
Federica Agostini, Jan-Stefan Völler, Beate Koksch, Carlos G. Acevedo-Rocha, Vladimir Kubyshkin, Nediljko Budisa. Biocatalysis with Unnatural Amino Acids: Enzymology Meets Xenobiology. Angewandte Chemie International Edition 2017, 56 (33) , 9680-9703. DOI: 10.1002/anie.201610129.
Stéphane Romero, François-Xavier Campbell-Valois. Proteins. 2017,,, 59-92. DOI: 10.1002/9781118942246.ch2.4.
Yu-Cheng Zhou, Min Zhao, Yan-Qing Yu, Yan-Mei Lei, Ya-Qin Chai, Ruo Yuan, Ying Zhuo. Three-dimensional nano-network composed of Pt nanoparticles functionalized Mn-doped CeO2 and hemin/G-quadruplex as electrocatalysts for cardiovascular biomarker detection. Sensors and Actuators B: Chemical 2017, 246, 1-8. DOI: 10.1016/j.snb.2017.02.047.
Christian B Rosen, Matthew B Francis. Targeting the N terminus for site-selective protein modification. Nature Chemical Biology 2017, 13 (7) , 697-705. DOI: 10.1038/nchembio.2416.
Jiří Václavík, Reinhard Zschoche, Iveta Klimánková, Václav Matoušek, Petr Beier, Donald Hilvert, Antonio Togni. Irreversible Cysteine-Selective Protein Labeling Employing Modular Electrophilic Tetrafluoroethylation Reagents. Chemistry - A European Journal 2017, 23 (27) , 6490-6494. DOI: 10.1002/chem.201700607.
Omar Boutureira, Nuria Martínez-Sáez, Kevin M. Brindle, André A. Neves, Francisco Corzana, Gonçalo J. L. Bernardes. Site-Selective Modification of Proteins with Oxetanes. Chemistry - A European Journal 2017, 23 (27) , 6483-6489. DOI: 10.1002/chem.201700745.
Ján Lauko, Paul H. J. Kouwer, Alan E. Rowan. 1 H -1,2,3-Triazole: From Structure to Function and Catalysis. Journal of Heterocyclic Chemistry 2017, 54 (3) , 1677-1699. DOI: 10.1002/jhet.2770.
Filipe Natalio, Stefanie Wiese, Wolfgang Brandt, Ludger Wessjohann. Reconstitution of Vanadium Haloperoxidase's Catalytic Activity by Boric Acid-Towards a Potential Biocatalytic Role of Boron. Chemistry - A European Journal 2017, 23 (21) , 4973-4980. DOI: 10.1002/chem.201605230.
Saumitra Sengupta, Goverdhan Mehta. Late stage modification of peptides via C H activation reactions. Tetrahedron Letters 2017, 58 (14) , 1357-1372. DOI: 10.1016/j.tetlet.2017.02.069.
Maheshwerreddy Chilamari, Landa Purushottam, Vishal Rai. Site-Selective Labeling of Native Proteins by a Multicomponent Approach. Chemistry - A European Journal 2017, 23 (16) , 3819-3823. DOI: 10.1002/chem.201605938.
Hong Geun Lee, Guillaume Lautrette, Bradley L. Pentelute, Stephen L. Buchwald. Palladium-Mediated Arylation of Lysine in Unprotected Peptides. Angewandte Chemie 2017, 129 (12) , 3225-3229. DOI: 10.1002/ange.201611202.
Hong Geun Lee, Guillaume Lautrette, Bradley L. Pentelute, Stephen L. Buchwald. Palladium-Mediated Arylation of Lysine in Unprotected Peptides. Angewandte Chemie International Edition 2017, 56 (12) , 3177-3181. DOI: 10.1002/anie.201611202.
Jason E. Hein. [3+2]-Dipolar Cycloadditions in Bioconjugation. 2017,,, 37-66. DOI: 10.1002/9783527683451.ch2.
Justin M. Chalker. Metal-Mediated Bioconjugation. 2017,,, 231-270. DOI: 10.1002/9783527683451.ch8.
Eric Defrancq, Samir Messaoudi. Palladium-Mediated Labeling of Nucleic Acids. ChemBioChem 2017, 18 (5) , 426-431. DOI: 10.1002/cbic.201600599.
Shixian Lin, Xiaoyu Yang, Shang Jia, Amy M. Weeks, Michael Hornsby, Peter S. Lee, Rita V. Nichiporuk, Anthony T. Iavarone, James A. Wells, F. Dean Toste, Christopher J. Chang. Redox-based reagents for chemoselective methionine bioconjugation. Science 2017, 355 (6325) , 597-602. DOI: 10.1126/science.aal3316.
Arcadio Vázquez, Rastislav Dzijak, Martin Dračínský, Robert Rampmaier, Sebastian J. Siegl, Milan Vrabel. Mechanism-Based Fluorogenic trans -Cyclooctene-Tetrazine Cycloaddition. Angewandte Chemie 2017, 129 (5) , 1354-1357. DOI: 10.1002/ange.201610491.
Arcadio Vázquez, Rastislav Dzijak, Martin Dračínský, Robert Rampmaier, Sebastian J. Siegl, Milan Vrabel. Mechanism-Based Fluorogenic trans -Cyclooctene-Tetrazine Cycloaddition. Angewandte Chemie International Edition 2017, 56 (5) , 1334-1337. DOI: 10.1002/anie.201610491.
Linghui Qian, Chong-Jing Zhang, Ji'en Wu, Shao Q. Yao. Fused Bicyclic Caspase-1 Inhibitors Assembled by Copper-Free Strain-Promoted Alkyne-Azide Cycloaddition (SPAAC). Chemistry - A European Journal 2017, 23 (2) , 360-369. DOI: 10.1002/chem.201603150.
Matthias P. Exner, Tilmann Kuenzl, Tuyet Mai T. To, Zhaofei Ouyang, Sergej Schwagerus, Michael G. Hoesl, Christian P. R. Hackenberger, Marga C. Lensen, Sven Panke, Nediljko Budisa. Design of S -Allylcysteine in Situ Production and Incorporation Based on a Novel Pyrrolysyl-tRNA Synthetase Variant. ChemBioChem 2017, 18 (1) , 85-90. DOI: 10.1002/cbic.201600537.
Veronika Ulrich, Max J. Cryle. SNaPe: a versatile method to generate multiplexed protein fusions using synthetic linker peptides for in vitro applications. Journal of Peptide Science 2017, 23 (1) , 16-27. DOI: 10.1002/psc.2943.
Takenori Tomohiro. Tag-Creation Approaches for Highly Efficient Profiling of Interacting Proteins and Domains. 2017,,, 13-43. DOI: 10.1007/978-4-431-56569-7_2.
Amit Kumar, Jason White, R. James Christie, Nazzareno Dimasi, Changshou Gao. Antibody-Drug Conjugates. 2017,,, 441-480. DOI: 10.1016/bs.armc.2017.08.002.
Jayasubba Reddy Yarava, Rajesh Sonti, K. Kantharaju, S. Raghothama, K. V. Ramanathan. Solid-state NMR at natural isotopic abundance for the determination of conformational polymorphism – the case of designed β-turn peptides containing di-prolines. Chemical Communications 2017, 53 (7) , 1317-1320. DOI: 10.1039/C6CC08676D.
P. Wilke, T. Kunde, S. Chattopadhyay, N. ten Brummelhuis, F. E. Du Prez, H. G. Börner. Easy access to triazolinedione-endcapped peptides for chemical ligation. Chemical Communications 2017, 53 (3) , 593-596. DOI: 10.1039/C6CC08683G.
Jun Ohata, Zachary T. Ball. Ascorbate as a pro-oxidant: mild N-terminal modification with vinylboronic acids. Chemical Communications 2017, 53 (10) , 1622-1625. DOI: 10.1039/C6CC09955F.
Wen-Bin Zhang, Xia-Ling Wu, Guang-Zhong Yin, Yu Shao, Stephen Z. D. Cheng. From protein domains to molecular nanoparticles: what can giant molecules learn from proteins?. Materials Horizons 2017, 4 (2) , 117-132. DOI: 10.1039/C6MH00448B.
T. Wezeman, J. Comas-Barceló, M. Nieger, J. P. A. Harrity, S. Bräse. Synthesis of aminopyrazoles from sydnones and ynamides. Organic & Biomolecular Chemistry 2017, 15 (7) , 1575-1579. DOI: 10.1039/C6OB02518H.
Daniel A. Richards, Antoine Maruani, Vijay Chudasama. Antibody fragments as nanoparticle targeting ligands: a step in the right direction. Chemical Science 2017, 8 (1) , 63-77. DOI: 10.1039/C6SC02403C.
M. J. Corr, S. V. Sharma, C. Pubill-Ulldemolins, R. T. Bown, P. Poirot, D. R. M. Smith, C. Cartmell, A. Abou Fayad, R. J. M. Goss. Sonogashira diversification of unprotected halotryptophans, halotryptophan containing tripeptides; and generation of a new to nature bromo-natural product and its diversification in water. Chemical Science 2017, 8 (3) , 2039-2046. DOI: 10.1039/C6SC04423A.
Terence T.-L. Kwan, Omar Boutureira, Elizabeth C. Frye, Stephen J. Walsh, Moni K. Gupta, Stephen Wallace, Yuteng Wu, Fengzhi Zhang, Hannah F. Sore, Warren R. J. D. Galloway, Jason W. Chin, Martin Welch, Gonçalo J. L. Bernardes, David R. Spring. Protein modification via alkyne hydrosilylation using a substoichiometric amount of ruthenium( ii ) catalyst. Chemical Science 2017, 8 (5) , 3871-3878. DOI: 10.1039/C6SC05313K.
Gosuke Hayashi, Naoki Kamo, Akimitsu Okamoto. Chemical synthesis of dual labeled proteins via differently protected alkynes enables intramolecular FRET analysis. Chemical Communications 2017, 53 (43) , 5918-5921. DOI: 10.1039/C7CC02612A.
B. L. Oliveira, Z. Guo, G. J. L. Bernardes. Inverse electron demand Diels–Alder reactions in chemical biology. Chemical Society Reviews 2017, 46 (16) , 4895-4950. DOI: 10.1039/C7CS00184C.
João H. P. M. Santos, Gustavo Carretero, João A. P. Coutinho, Carlota O. Rangel-Yagui, Sónia P. M. Ventura. Multistep purification of cytochrome c PEGylated forms using polymer-based aqueous biphasic systems. Green Chemistry 2017, 19 (24) , 5800-5808. DOI: 10.1039/C7GC02600E.
Diana Gimenez, Caitlin A. Mooney, Anica Dose, Graham Sandford, Christopher R. Coxon, Steven L. Cobb. The application of perfluoroheteroaromatic reagents in the preparation of modified peptide systems. Organic & Biomolecular Chemistry 2017, 15 (19) , 4086-4095. DOI: 10.1039/C7OB00283A.
Vivian Triana, Ratmir Derda. Tandem Wittig/Diels–Alder diversification of genetically encoded peptide libraries. Organic & Biomolecular Chemistry 2017, 15 (37) , 7869-7877. DOI: 10.1039/C7OB01635B.
Hongli Chen, Rong Huang, Zhihong Li, Wei Zhu, Jiakang Chen, Yuexiong Zhan, Biao Jiang. Selective lysine modification of native peptides via aza-Michael addition. Organic & Biomolecular Chemistry 2017, 15 (35) , 7339-7345. DOI: 10.1039/C7OB01866E.
João M. J. M. Ravasco, Carlos M. Monteiro, Alexandre F. Trindade. Cyclopropenes: a new tool for the study of biological systems. Organic Chemistry Frontiers 2017, 4 (6) , 1167-1198. DOI: 10.1039/C7QO00054E.
Kuldeep Bansal, Luana Sasso, Hiteshri Makwana, Sahar Awwad, Steve Brocchini, Cameron Alexander. Nanopharmacy: Exploratory Methods for Polymeric Materials. 2016,,, 231-270. DOI: 10.1002/9783527800681.ch10.
Barbara Bernardim, Pedro M.S.D. Cal, Maria J. Matos, Bruno L. Oliveira, Nuria Martínez-Sáez, Inês S. Albuquerque, Elizabeth Perkins, Francisco Corzana, Antonio C.B. Burtoloso, Gonzalo Jiménez-Osés, Gonçalo J. L. Bernardes. Stoichiometric and irreversible cysteine-selective protein modification using carbonylacrylic reagents. Nature Communications 2016, 7 (1) DOI: 10.1038/ncomms13128.
Xiaoguang Zhang, Peiye Liu, Lei Zhu. Structural Determinants of Alkyne Reactivity in Copper-Catalyzed Azide-Alkyne Cycloadditions. Molecules 2016, 21 (12) , 1697. DOI: 10.3390/molecules21121697.
Seah Ling Kuan, Tao Wang, Tanja Weil. Site-Selective Disulfide Modification of Proteins: Expanding Diversity beyond the Proteome. Chemistry - A European Journal 2016, 22 (48) , 17112-17129. DOI: 10.1002/chem.201602298.
David P Fairlie, Aline Dantas de Araujo. Stapling peptides using cysteine crosslinking. Biopolymers 2016, 106 (6) , 843-852. DOI: 10.1002/bip.22877.
Naipu He, Yue Wang, Zhenwu Lu. Temperature-responsive “tadpole-shaped” protein-polymer hybrids and their self-assembly behavior. Polymers for Advanced Technologies 2016, 27 (10) , 1376-1382. DOI: 10.1002/pat.3806.
Puzhou Wang, Scott K. Silverman. DNA-Catalyzed Introduction of Azide at Tyrosine for Peptide Modification. Angewandte Chemie 2016, 128 (34) , 10206-10210. DOI: 10.1002/ange.201604364.
Puzhou Wang, Scott K. Silverman. DNA-Catalyzed Introduction of Azide at Tyrosine for Peptide Modification. Angewandte Chemie International Edition 2016, 55 (34) , 10052-10056. DOI: 10.1002/anie.201604364.
Riyadh Ahmed Atto Al-Shuaeeb, Sergii Kolodych, Oleksandr Koniev, Sébastien Delacroix, Stéphane Erb, Stéphanie Nicolaÿ, Jean-Christophe Cintrat, Jean-Daniel Brion, Sarah Cianférani, Mouâd Alami, Alain Wagner, Samir Messaoudi. Palladium-Catalyzed Chemoselective and Biocompatible Functionalization of Cysteine-Containing Molecules at Room Temperature. Chemistry - A European Journal 2016, 22 (32) , 11365-11370. DOI: 10.1002/chem.201602277.
Akihiro Ogura, Almira Kurbangalieva, Katsunori Tanaka. Exploring the glycan interaction in vivo: Future prospects of neo-glycoproteins for diagnostics. Glycobiology 2016, 26 (8) , 804-812. DOI: 10.1093/glycob/cww038.
Cecilia Bottecchia, Nico Erdmann, Patricia M. A. Tijssen, Lech-Gustav Milroy, Luc Brunsveld, Volker Hessel, Timothy Noël. Batch and Flow Synthesis of Disulfides by Visible-Light-Induced TiO 2 Photocatalysis. ChemSusChem 2016, 9 (14) , 1781-1785. DOI: 10.1002/cssc.201600602.
Eric A. Hunt, Angeliki Moutsiopoulou, Stephanie Ioannou, Katelyn Ahern, Kristen Woodward, Emre Dikici, Sylvia Daunert, Sapna K. Deo. Truncated Variants of Gaussia Luciferase with Tyrosine Linker for Site-Specific Bioconjugate Applications. Scientific Reports 2016, 6 (1) DOI: 10.1038/srep26814.
Hui Jian, Yingwu Wang, Yan Bai, Rong Li, Renjun Gao. Site-Specific, Covalent Immobilization of Dehalogenase ST2570 Catalyzed by Formylglycine-Generating Enzymes and Its Application in Batch and Semi-Continuous Flow Reactors. Molecules 2016, 21 (7) , 895. DOI: 10.3390/molecules21070895.
Steve Knutson, Erum Raja, Ryan Bomgarden, Marie Nlend, Aoshuang Chen, Ramaswamy Kalyanasundaram, Surbhi Desai, . Development and Evaluation of a Fluorescent Antibody-Drug Conjugate for Molecular Imaging and Targeted Therapy of Pancreatic Cancer. PLOS ONE 2016, 11 (6) , e0157762. DOI: 10.1371/journal.pone.0157762.
Eirini Antonatou, Kurt Hoogewijs, Dimitris Kalaitzakis, Andreas Baudot, Georgios Vassilikogiannakis, Annemieke Madder. Singlet Oxygen-Induced Furan Oxidation for Site-Specific and Chemoselective Peptide Ligation. Chemistry - A European Journal 2016, 22 (25) , 8457-8461. DOI: 10.1002/chem.201601113.
Yanyan Jiang, Martina Stenzel. Drug Delivery Vehicles Based on Albumin-Polymer Conjugates. Macromolecular Bioscience 2016, 16 (6) , 791-802. DOI: 10.1002/mabi.201500453.
Changlong Wang, Djamila Ikhlef, Samia Kahlal, Jean-Yves Saillard, Didier Astruc. Metal-catalyzed azide-alkyne “click” reactions: Mechanistic overview and recent trends. Coordination Chemistry Reviews 2016, 316, 1-20. DOI: 10.1016/j.ccr.2016.02.010.
T. Qin, J. Cornella, C. Li, L. R. Malins, J. T. Edwards, S. Kawamura, B. D. Maxwell, M. D. Eastgate, P. S. Baran. A general alkyl-alkyl cross-coupling enabled by redox-active esters and alkylzinc reagents. Science 2016, 352 (6287) , 801-805. DOI: 10.1126/science.aaf6123.
Takuya Machida, Nicolas Winssinger. One-Step Derivatization of Reducing Oligosaccharides for Rapid and Live-Cell-Compatible Chelation-Assisted CuAAC Conjugation. ChemBioChem 2016, 17 (9) , 811-815. DOI: 10.1002/cbic.201600003.
Jennifer J. McManus, Patrick Charbonneau, Emanuela Zaccarelli, Neer Asherie. The physics of protein self-assembly. Current Opinion in Colloid & Interface Science 2016, 22, 73-79. DOI: 10.1016/j.cocis.2016.02.011.
Matthias Exner, Sebastian Köhling, Julie Rivollier, Sandrine Gosling, Puneet Srivastava, Zheni Palyancheva, Piet Herdewijn, Marie-Pierre Heck, Jörg Rademann, Nediljko Budisa. Incorporation of Amino Acids with Long-Chain Terminal Olefins into Proteins. Molecules 2016, 21 (3) , 287. DOI: 10.3390/molecules21030287.
Thomas Carell, Milan Vrabel. Bioorthogonal Chemistry—Introduction and Overview. Topics in Current Chemistry 2016, 374 (1) DOI: 10.1007/s41061-016-0010-x.
Dimpy Kalia, Pushpa V. Malekar, Manikandan Parthasarathy. Exocyclic Olefinic Maleimides: Synthesis and Application for Stable and Thiol-Selective Bioconjugation. Angewandte Chemie 2016, 128 (4) , 1454-1457. DOI: 10.1002/ange.201508118.
Dimpy Kalia, Pushpa V. Malekar, Manikandan Parthasarathy. Exocyclic Olefinic Maleimides: Synthesis and Application for Stable and Thiol-Selective Bioconjugation. Angewandte Chemie International Edition 2016, 55 (4) , 1432-1435. DOI: 10.1002/anie.201508118.
R. Gianatassio, J. M. Lopchuk, J. Wang, C.-M. Pan, L. R. Malins, L. Prieto, T. A. Brandt, M. R. Collins, G. M. Gallego, N. W. Sach, J. E. Spangler, H. Zhu, J. Zhu, P. S. Baran. Strain-release amination. Science 2016, 351 (6270) , 241-246. DOI: 10.1126/science.aad6252.
Henning Stöckmann, Violeta L. Marin, Paul Nimmer, Corina M. Balut, Donald J. Davidson, Paul L. Richardson, Anil Vasudevan. Glycan-Mediated, Ligand-Controlled Click Chemistry for Drug-Target Identification. ChemBioChem 2016, 17 (2) , 150-154. DOI: 10.1002/cbic.201500590.
Z. Wang, L.A. Campos, V. Muñoz. Single-Molecule Fluorescence Studies of Fast Protein Folding. 2016,,, 417-459. DOI: 10.1016/bs.mie.2016.09.011.
Michael Clinton Koetting, Joseph Frank Guido, Malvika Gupta, Annie Zhang, Nicholas A. Peppas. pH-responsive and enzymatically-responsive hydrogel microparticles for the oral delivery of therapeutic proteins: Effects of protein size, crosslinking density, and hydrogel degradation on protein delivery. Journal of Controlled Release 2016, 221, 18-25. DOI: 10.1016/j.jconrel.2015.11.023.
Jiandong Wang, Pingfan Li, Zhanhui Yang, Ning Chen, Jiaxi Xu. Insights into the diastereoselective control in the sulfa-Michael addition of thiols to nitroalkenes: stereoelectronic effect in the cyclic chelated transition state. Tetrahedron 2016, 72 (3) , 370-378. DOI: 10.1016/j.tet.2015.11.030.
Qi-Ying Hu, Francesco Berti, Roberto Adamo. Towards the next generation of biomedicines by site-selective conjugation. Chemical Society Reviews 2016, 45 (6) , 1691-1719. DOI: 10.1039/C4CS00388H.
Shan Zhao, Jianye Dai, Mo Hu, Chang Liu, Rong Meng, Xiaoyun Liu, Chu Wang, Tuoping Luo. Photo-induced coupling reactions of tetrazoles with carboxylic acids in aqueous solution: application in protein labelling. Chemical Communications 2016, 52 (25) , 4702-4705. DOI: 10.1039/C5CC10445A.
Maximillian T. W. Lee, Antoine Maruani, James R. Baker, Stephen Caddick, Vijay Chudasama. Next-generation disulfide stapling: reduction and functional re-bridging all in one. Chemical Science 2016, 7 (1) , 799-802. DOI: 10.1039/C5SC02666K.
Richard C. Brewster, Georgina C. Gavins, Barbara Günthardt, Sarah Farr, Kimberly M. Webb, Philipp Voigt, Alison N. Hulme. Chloromethyl-triazole: a new motif for site-selective pseudo-acylation of proteins. Chemical Communications 2016, 52 (82) , 12230-12232. DOI: 10.1039/C6CC06801D.
D. Madea, T. Slanina, P. Klán. A ‘photorelease, catch and photorelease’ strategy for bioconjugation utilizing a p-hydroxyphenacyl group. Chemical Communications 2016, 52 (87) , 12901-12904. DOI: 10.1039/C6CC07496K.
Chih-Chi Chu, Scott K. Silverman. Assessing histidine tags for recruiting deoxyribozymes to catalyze peptide and protein modification reactions. Organic & Biomolecular Chemistry 2016, 14 (20) , 4697-4703. DOI: 10.1039/C6OB00716C.
Richard J. Spears, Martin A. Fascione. Site-selective incorporation and ligation of protein aldehydes. Organic & Biomolecular Chemistry 2016, 14 (32) , 7622-7638. DOI: 10.1039/C6OB00778C.
Katsunori Tanaka. Chemically synthesized glycoconjugates on proteins: effects of multivalency and glycoform in vivo. Organic & Biomolecular Chemistry 2016, 14 (32) , 7610-7621. DOI: 10.1039/C6OB00788K.
Smita B. Gunnoo, Annemieke Madder. Bioconjugation – using selective chemistry to enhance the properties of proteins and peptides as therapeutics and carriers. Organic & Biomolecular Chemistry 2016, 14 (34) , 8002-8013. DOI: 10.1039/C6OB00808A.
Antoine Maruani, Daniel A. Richards, Vijay Chudasama. Dual modification of biomolecules. Organic & Biomolecular Chemistry 2016, 14 (26) , 6165-6178. DOI: 10.1039/C6OB01010E.
Padma Akkapeddi, Saara-Anne Azizi, Allyson M. Freedy, Pedro M. S. D. Cal, Pedro M. P. Gois, Gonçalo J. L. Bernardes. Construction of homogeneous antibody–drug conjugates using site-selective protein chemistry. Chemical Science 2016, 7 (5) , 2954-2963. DOI: 10.1039/C6SC00170J.
Hélio Faustino, Maria J. S. A. Silva, Luís F. Veiros, Gonçalo J. L. Bernardes, Pedro M. P. Gois. Iminoboronates are efficient intermediates for selective, rapid and reversible N-terminal cysteine functionalisation. Chemical Science 2016, 7 (8) , 5052-5058. DOI: 10.1039/C6SC01520D.
Gergely L Tolnai, Jonathan P Brand, Jerome Waser. Gold-catalyzed direct alkynylation of tryptophan in peptides using TIPS-EBX. Beilstein Journal of Organic Chemistry 2016, 12, 745-749. DOI: 10.3762/bjoc.12.74.
Yuki Nishikawa, Tomonori Tamura, Itaru Hamachi. Recent Advance in Organic Chemistry for Protein Labeling under Live Cell Conditions. Journal of Synthetic Organic Chemistry, Japan 2016, 74 (5) , 521-531. DOI: 10.5059/yukigoseikyokaishi.74.521.
Marcel Wirtz, Andreas Grüter, Florian Heib, Volker Huch, Josef Zapp, Dirk-Peter Herten, Michael Schmitt, Gregor Jung. A two-color fluorogenic carbene complex for tagging olefins via metathesis reaction. Methods and Applications in Fluorescence 2015, 3 (4) , 044001. DOI: 10.1088/2050-6120/3/4/044001.
Giuseppe Stefanetti, Qi‐Ying Hu, Aimee Usera, Zack Robinson, Martin Allan, Alok Singh, Hidetomo Imase, Jennifer Cobb, Huili Zhai, Douglas Quinn, Ming Lei, Allan Saul, Roberto Adamo, Calman A. MacLennan, Francesca Micoli. Sugar–Protein Connectivity Impacts on the Immunogenicity of Site‐Selective Salmonella O‐Antigen Glycoconjugate Vaccines. Angewandte Chemie 2015, 127 (45) , 13396-13401. DOI: 10.1002/ange.201506112.
Giuseppe Stefanetti, Qi-Ying Hu, Aimee Usera, Zack Robinson, Martin Allan, Alok Singh, Hidetomo Imase, Jennifer Cobb, Huili Zhai, Douglas Quinn, Ming Lei, Allan Saul, Roberto Adamo, Calman A. MacLennan, Francesca Micoli. Sugar-Protein Connectivity Impacts on the Immunogenicity of Site-Selective Salmonella O-Antigen Glycoconjugate Vaccines. Angewandte Chemie International Edition 2015, 54 (45) , 13198-13203. DOI: 10.1002/anie.201506112.
Jitka Dadová, Milan Vrábel, Matej Adámik, Marie Brázdová, Radek Pohl, Miroslav Fojta, Michal Hocek. Azidopropylvinylsulfonamide as a New Bifunctional Click Reagent for Bioorthogonal Conjugations: Application for DNA-Protein Cross-Linking. Chemistry - A European Journal 2015, 21 (45) , 16091-16102. DOI: 10.1002/chem.201502209.
Conor M Haney, Rebecca F Wissner, E James Petersson. Multiply labeling proteins for studies of folding and stability. Current Opinion in Chemical Biology 2015, 28, 123-130. DOI: 10.1016/j.cbpa.2015.07.007.
Heather Maynard. Protein modification in a trice. Nature 2015, 526 (7575) , 646-647. DOI: 10.1038/526646b.
Thi Minh Nguyet Trinh, Thanh Tung Nguyen, Cyril Kopp, Pauline Pieper, Virginie Russo, Benoît Heinrich, Bertrand Donnio, Thi Le Anh Nguyen, Robert Deschenaux. Olefin Cross-Metathesis: a Versatile Synthetic Reaction for the Design of Janus Liquid Crystals. European Journal of Organic Chemistry 2015, 2015 (27) , 6005-6010. DOI: 10.1002/ejoc.201500754.
Shin-nosuke Uno, Dhermendra K. Tiwari, Mako Kamiya, Yoshiyuki Arai, Takeharu Nagai, Yasuteru Urano. A guide to use photocontrollable fluorescent proteins and synthetic smart fluorophores for nanoscopy. Microscopy 2015, 64 (4) , 263-277. DOI: 10.1093/jmicro/dfv037.
M. K. Quinn, N. Gnan, S. James, A. Ninarello, F. Sciortino, E. Zaccarelli, J. J. McManus. How fluorescent labelling alters the solution behaviour of proteins. Physical Chemistry Chemical Physics 2015, 17 (46) , 31177-31187. DOI: 10.1039/C5CP04463D.
Hamid Marzag, Soukaina Alaoui, Hella Amdouni, Anthony R. Martin, Khalid Bougrin, Rachid Benhida. Efficient and selective azidation of per-O-acetylated sugars using ultrasound activation: application to the one-pot synthesis of 1,2,3-triazole glycosides. New Journal of Chemistry 2015, 39 (7) , 5437-5444. DOI: 10.1039/C5NJ00624D.
Jie Zhang, Yuwen Men, Shanshan Lv, Long Yi, Jian-Feng Chen. Protein tetrazinylation via diazonium coupling for covalent and catalyst-free bioconjugation. Organic & Biomolecular Chemistry 2015, 13 (47) , 11422-11425. DOI: 10.1039/C5OB02053K.
J. A. Denny, W. S. Foley, A. D. Todd, M. Y. Darensbourg. The ligand unwrapping/rewrapping pathway that exchanges metals in S-acetylated, hexacoordinate N 2 S 2 O 2 complexes. Chemical Science 2015, 6 (12) , 7079-7088. DOI: 10.1039/C5SC02269J.

Abstract
High Resolution Image
Download MS PowerPoint Slide
Scheme 1
Scheme 1. Classical Methods for the Modification of Cys and Lys: (a) Amide Formation, (b) Urea and Thiourea Formation, (c) Reductive Amination, (d) Cys-Specific Disulfide Exchange, (e) Alkylation, and (f) Conjugate Addition to a Representative Maleimide Michael Acceptor
High Resolution Image
Download MS PowerPoint Slide
Scheme 2
Scheme 2. Recent Site-Selective Methods for the Modification of Lys and the N-Terminal Position: (a) Lys Labeling by Rapid 6π-Aza-electrocyclization Reaction or (b) 2-Imino-2-methoxyethyl Reagents (IME), (c) Reversible Lys and N-Terminal Modification via Formation of Stable Iminobornates, (D) Reaction With Diazonium Salts, and (e) Selective N-Terminal Modification Using Ketenes
High Resolution Image
Download MS PowerPoint Slide
Scheme 3
Scheme 3. Recent Site-Selective Methods for the Modification of Tyr: (a) Reaction with Diazonium Salts, (b) Three-Component Mannich Reaction, (c) Reaction with Preformed Imines, and (d) Ene-type Reaction with Diazodicarboxylate Reagents
High Resolution Image
Download MS PowerPoint Slide
Scheme 4
Scheme 4. Site-Selective Chemical Protein Modification at Cys and Dha: (a) Nucleophilic Disulfide Formation, (b) Diselenide Exchange, (c) Electrophilic Disulfide Formation, (d) Thioether Formation
High Resolution Image
Download MS PowerPoint Slide
Scheme 5
Scheme 5. Site-Selective Modification of Antibodies at Cys (a) at the C-Terminus via Disulfide and (b) at the N-Terminus via Thiazolidine
High Resolution Image
Download MS PowerPoint Slide
Scheme 6
Scheme 6. Site-Selective Methods for Cys Modification Using Polar Reactions—Part A: (a) Bromo- (X = H, Y = Br), Dibromo- (X = Y = Br), and Aryloxy- (X = H, Y = OAr) Maleimides, (b) Bromo- (X = H) and Dibromo- (X = Br) Pyridazinediones, (c) Dibromo Bisamide (2,5-Dibromohexanediamide) and Addition to the Electron-Deficient Triple Bonds (d) Alkynones and (e) 3-Arylpropiolonitriles
High Resolution Image
Download MS PowerPoint Slide
Scheme 7
Scheme 7. Site-Selective Methods for Cys Modification Using Polar Reactions—Part B: (e) 3-(Hydroxymethyl)-2-naphthol, (f) Julia–Kocienski-like Reagents, and (g) Addition to Allenamides
High Resolution Image
Download MS PowerPoint Slide
Scheme 8
Scheme 8. Site-Selective Methods for Cys Modification Using Radical (a) Thiol–Ene and (b) Thiol–Yne Reactions
High Resolution Image
Download MS PowerPoint Slide
Scheme 9
Scheme 9. Chemical Synthesis of Uniformly Sized Cyclic Peptides by Selective Cys Alkylation with (a) Electrophilic Trihalides and (b) Perfluorinated Benzene Derivatives. GST = Glutathione S-Transferase, TCEP = Tris(2-carboxyethyl)phosphine
High Resolution Image
Download MS PowerPoint Slide
Scheme 10
Scheme 10. Site-Selective Methods for the Modification of Exposed Disulfides: Bis-alkylation with (a) α,β-Unsaturated-β′-monosulfones and (b) Dibromo/Dithiophenol (X = Y = Br, SPh) or Aryloxy (X = H, Y = OAr) Maleimides
High Resolution Image
Download MS PowerPoint Slide
Scheme 11
Scheme 11. Bioorthogonal Reactions at Ketone and Aldehyde Functionalities: (a) Oxime and (b) Hydrazone Formation, (c) Pictet–Spengler Reaction and Its Improved Versions (d) Pictet–Spengler Ligation (X = O) and Hydrazino-Pictet–Spengler Ligation (X = NHMe), (e) Wittig Reaction
High Resolution Image
Download MS PowerPoint Slide
Scheme 12
Scheme 12. Metal-Free Bioorthogonal Reactions at Azides: (a) Staudinger, (b) Traceless Staudinger and (c) Staudinger-Phosphite/Phosphonite Ligations, and (d) Strain-Promoted Cycloadditions
High Resolution Image
Download MS PowerPoint Slide
Scheme 13
Scheme 13. Metal-Free Bioorthogonal Reactions at Other Dipole Handles: (a) Nitrones, (b) Nitrile Oxides and (c) 4-Halosydnones with Cyclooctyne (Metal-Free Click Reactions), and (d) Isonitriles with Tetrazine
High Resolution Image
Download MS PowerPoint Slide
Scheme 14
Scheme 14. Metal-Free Bioorthogonal Reactions at Alkynes and Cyclooctynes: (a) Thiol–Yne and Strain-Promoted Cycloadditions with (b) Azides, (c) Tetrazines, and (d) Sydnones
High Resolution Image
Download MS PowerPoint Slide
Scheme 15
Scheme 15. Metal-Free Bioorthogonal Reactions at Alkenes: (a, b) Reactions of Oxanorbornadienes and Norbornenes with Azides, (c) Inverse-Demand Diels–Alder of trans-Cyclooctenes and (d) Norbornenes and 1,3-Cyclopropenes with Tetrazines, (e) In Situ Nitrile Imine Generation from Hydrazonoyl Chloride and (f, g) Tetrazole and Subsequent 1,3-Dipolar Cycloaddition with Alkenes Including 3,3-Cyclopropenes and Spiro[2.3]hex-1-ene; (h) Thiol–Ene, and (i) Hetero-Diels–Alder with Vinyl Sulfides
High Resolution Image
Download MS PowerPoint Slide
Scheme 16
Scheme 16. Metal-Free Bioorthogonal Reactions at Dienes and Maleimides: (a) Classical Diels–Alder Reaction and (b) the Kondrat’eva Hetero-Diels–Alder Irreversible Ligation
High Resolution Image
Download MS PowerPoint Slide
Scheme 17
Scheme 17. Lysine and Tyrosine Modifications with Iridium and Palladium Complexes: (a) Reductive Alkylation of Lysine and N-Terminus with Ir Complex and (b) Pd-Catalyzed Allylic O-Alkylation of Tyrosine
High Resolution Image
Download MS PowerPoint Slide
Scheme 18
Scheme 18. Metal-Mediated Tryptophan, Cysteine, and “Proximity-Driven or Recognition” Modifications: (a–c) Modifications with Rhodium Carbenoids and (d) Au-Catalyzed Oxidative Allene–Thiol Coupling of Cysteine
High Resolution Image
Download MS PowerPoint Slide
Scheme 19
Scheme 19. Transition Metal-Mediated Modifications of Sydnones and Azides: (a–c) Cu(I)- and Ru(II)-Catalyzed Azide–Alkyne and Sydnone Cycloadditions, Respectively
High Resolution Image
Download MS PowerPoint Slide
Scheme 20
Scheme 20. Transition Metal-Mediated Modifications of Alkynes: (a, b) Cu(I)- and Ru(II)-Catalyzed Azide–Alkyne Cycloadditions, Respectively, (c) Copper-Free Sonogashira Cross-Coupling at Homopropargylglycine (Hpg) and Its (d) Ligandless Version at Pyrrolysine (Pyl)-Based Systems, (e) Modification of Hpg with Palladacycles
High Resolution Image
Download MS PowerPoint Slide
Scheme 21
Scheme 21. Transition Metal-Mediated Modification of Alkenes: Olefin Cross-Metathesis with (a) S-Allylcysteine and (b) Se-Allylselenocysteine, and (c) Pd-Catalyzed Oxidative Heck Reaction
High Resolution Image
Download MS PowerPoint Slide
Scheme 22
Scheme 22. Pd-Mediated Protein Cross-Couplings at Aryl Halides: (a) Mizoroki–Heck, (b) Sonogashira and (c) Copper-Free Ligandless Version, (d) Phosphine-Free Suzuki–Miyaura with ADHP or NHC Ligands, and (e) Ligandless Suzuki–Miyaura Cross-Couplings
High Resolution Image
Download MS PowerPoint Slide
Scheme 23
Scheme 23. Pd-Mediated Protein Cross-Couplings at Aryl Boronates: (a) Suzuki–Miyaura
High Resolution Image
Download MS PowerPoint Slide
References
ARTICLE SECTIONS
Jump To
This article references 189 other publications.
1. 1
  Stephanopoulos, N.; Francis, M. B. Nat. Chem. Biol. 2011, 7, 876
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  1
  Choosing an effective protein bioconjugation strategy
  Stephanopoulos, Nicholas; Francis, Matthew B.
  Nature Chemical Biology (2011), 7 (12), 876-884CODEN: NCBABT; ISSN:1552-4450. (Nature Publishing Group)
  A review. The collection of chem. techniques that can be used to attach synthetic groups to proteins has expanded substantially in recent years. Each of these approaches allows new protein targets to be addressed, leading to advances in biol. understanding, new protein-drug conjugates, targeted medical imaging agents and hybrid materials with complex functions. The protein modification reactions in current use vary widely in their inherent site selectivity, overall yields and functional group compatibility. Some are more amenable to large-scale bioconjugate prodn., and a no. of techniques can be used to label a single protein in a complex biol. mixt. This review examines the way in which exptl. circumstances influence one's selection of an appropriate protein modification strategy. It also provides a simple decision tree that can narrow down the possibilities in many instances. The review concludes with example studies that examine how this decision process has been applied in different contexts.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhsVOisbbP&md5=f635776ca8c147f5e2e1227f8eec29d8
2. 2
  Walsh, C. T.; Garneau-Tsodikova, S.; Gregory J. Gatto, J. Angew. Chem., Int. Ed. 2005, 44, 7342
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  2
  Protein posttranslational modifications: The chemistry of proteome diversifications
  Walsh, Christopher T.; Garneau-Tsodikova, Sylvie; Gatto, Gregory J., Jr.
  Angewandte Chemie, International Edition (2005), 44 (45), 7342-7372CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
  A review. The diversity of distinct covalent forms of proteins (the proteome) greatly exceeds the no. of proteins predicted by DNA coding capacities owing to directed post-translational modifications. Enzymes dedicated to such protein modifications include 500 human protein kinases, 150 protein phosphatases, and 500 proteases. The major types of protein covalent modifications, such as phosphorylation, acetylation, glycosylation, methylation, and ubiquitination, can be classified according to the type of amino acid side-chain modified, the category of the modifying enzyme, and the extent of reversibility. Chem. events such as protein splicing, green fluorescent protein (GFP) maturation, and proteasome autoactivation also represent post-translational modifications. An understanding of the scope and pattern of the many post-translational modifications in eukaryotic cells provides insight into the function and dynamics of proteome compns.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXhtlSms77N&md5=1e1ccf345916c39631a1cc83093de9b1
3. 3
  Kee, J.-M.; Muir, T. W. ACS Chem. Biol. 2011, 7, 44
  [ ACS Full Text ], Google Scholar
  There is no corresponding record for this reference.
4. 4
  Bernardes, G. J. L.; Chalker, J. M.; Davis, B. G. Chemical Protein Modification; Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim, Germany, 2010.
  [ Crossref], Google Scholar
  There is no corresponding record for this reference.
5. 5
  (a) Sun, S. B.; Schultz, P. G.; Kim, C. H. ChemBioChem. 2014, 15, 1721
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  5a
  Therapeutic Applications of an Expanded Genetic Code
  Sun, Sophie B.; Schultz, Peter G.; Kim, Chan Hyuk
  ChemBioChem (2014), 15 (12), 1721-1729CODEN: CBCHFX; ISSN:1439-4227. (Wiley-VCH Verlag GmbH & Co. KGaA)
  A review. To date, over 100 noncanonical amino acids (ncAAs) have been genetically encoded in living cells in order to expand the functional repertoire of the canonical 20 amino acids. More recently, this technol. has been expanded to the field of protein therapeutics, where traditional chem. methods typically result in heterogeneous mixts. of proteins. The site-specific incorporation of ncAAs with orthogonal chem. groups allows unprecedented control over the site of conjugation and the stoichiometry, thus facilitating the rational optimization of the biol. functions and/or pharmacokinetics of biologics. Herein, we discuss the recent contribution of ncAA technol. in enhancing the pharmacol. properties of current protein therapeutics as well as developing novel therapeutic modalities.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtFyhu7nL&md5=e13618035c3ccc5bed06a3e6cf55b8fe
  (b) Pelegri-O’Day, E. M.; Lin, E.-W.; Maynard, H. D. J. Am. Chem. Soc. 2014, 136, 14323
  [ ACS Full Text ], [ CAS], Google Scholar
  5b
  Therapeutic Protein-Polymer Conjugates: Advancing Beyond PEGylation
  Pelegri-O'Day, Emma M.; Lin, En-Wei; Maynard, Heather D.
  Journal of the American Chemical Society (2014), 136 (41), 14323-14332CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  A review. Protein-polymer conjugates are widely used as therapeutics. All Food and Drug Administration (FDA)-approved protein conjugates are covalently linked to poly(ethylene glycol) (PEG). These PEGylated drugs have longer half-lives in the bloodstream, leading to less frequent dosing, which is a significant advantage for patients. However, there are some potential drawbacks to PEG that are driving the development of alternatives. Polymers that display enhanced pharmacokinetic properties along with addnl. advantages such as improved stability or degradability will be important to advance the field of protein therapeutics. This perspective presents a summary of protein-PEG conjugates for therapeutic use and alternative technologies in various stages of development as well as suggestions for future directions. Established methods of producing protein-PEG conjugates and new approaches utilizing controlled radical polymn. are also covered.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsFCjsLfI&md5=784f96a81f2c6f6bfba8b4dadb31bdcb
  (c) Chari, R. V. J.; Miller, M. L.; Widdison, W. C. Angew. Chem., Int. Ed. 2014, 53, 3796
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  5c
  Antibody-Drug Conjugates: An Emerging Concept in Cancer Therapy
  Chari, Ravi V. J.; Miller, Michael L.; Widdison, Wayne C.
  Angewandte Chemie, International Edition (2014), 53 (15), 3796-3827CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
  A review. Traditional cancer chemotherapy is often accompanied by systemic toxicity to the patient. Monoclonal antibodies against antigens on cancer cells offer an alternative tumor-selective treatment approach. However, most monoclonal antibodies are not sufficiently potent to be therapeutically active on their own. Antibody-drug conjugates (ADCs) use antibodies to deliver a potent cytotoxic compd. selectively to tumor cells, thus improving the therapeutic index of chemotherapeutic agents. The recent approval of two ADCs, brentuximab vedotin and ado-trastuzumab emtansine, for cancer treatment has spurred tremendous research interest in this field. This Review touches upon the early efforts in the field, and describes how the lessons learned from the first-generation ADCs have led to improvements in every aspect of this technol., i.e., the antibody, the cytotoxic compd., and the linker connecting them, leading to the current successes. The design of ADCs currently in clin. development, and results from mechanistic studies and preclin. and clin. evaluation are discussed. Emerging technologies that seek to further advance this exciting area of research are also discussed.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXjtVGmsr0%253D&md5=fbfb2f843f516654ea7c0eb98949604c
  (d) Schumacher, D.; Hackenberger, C. P. R. Curr. Opin. Chem. Biol. 2014, 22, 62
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  5d
  More than add-on: chemoselective reactions for the synthesis of functional peptides and proteins
  Schumacher, Dominik; Hackenberger, Christian PR
  Current Opinion in Chemical Biology (2014), 22 (), 62-69CODEN: COCBF4; ISSN:1367-5931. (Elsevier B.V.)
  The quest to enlarge the mol. space of functional biomols. has led to the discovery of selective, mild and high-yielding chem. reactions for the modification of peptides and proteins. These conjugation methods have recently become even more advanced with the advent of modern biochem. techniques such as unnatural protein expression or enzymic reactions that allow the site-specific modification of proteins. Within this overview, we will highlight recent examples that describe the site-specific functionalization of proteins. These examples go beyond the straightforward attachment of a given functional moiety to the protein backbone by employing either an innovative linker-design or by novel conjugation chem., where the modification reaction itself is responsible for the (altered) functional behavior of the biomol. The examples covered herein include 'turn-on' probes for cellular imaging with low levels of background fluorescence, branched or cleavable polymer-protein conjugates of high stability within a cellular environment, the installation of natural occurring posttranslational modifications to help understand their role in complex cellular environments and finally the engineering of novel antibody drug conjugates to facilitate target specific drug release.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhs12nur7J&md5=cb567453613d1b16eeb6d8303b3db3ba
6. 6
  (a) Siman, P.; Brik, A. Org. Biomol. Chem. 2012, 10, 5684
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  6a
  Chemical and semisynthesis of posttranslationally modified proteins
  Siman, Peter; Brik, Ashraf
  Organic & Biomolecular Chemistry (2012), 10 (30), 5684-5697CODEN: OBCRAK; ISSN:1477-0520. (Royal Society of Chemistry)
  A review. Posttranslational modifications of proteins play crucial roles in health and disease by affecting numerous aspects of protein structure, function, stability and sub cellular localization. Yet understanding the effects of these modifications on several of these processes at the mol. level has been hindered by the lack of homogeneously modified proteins obtained via traditional biochem. and mol. biol. approaches. Moreover, the prepn. of such bioconjugates at a workable level is highly demanding. Recent advances in protein chem. applying chem. and semisynthetic approaches are becoming increasingly beneficial to overcome these challenges. These methods allow site-specific modifications of a desired protein and afford the product in large quantities for biochem. and structural analyses. In this review, the authors survey these efforts and their importance in dissecting the role of several posttranslational modifications in various proteins. Several examples are presented where glycosylated, phosphorylated, ubiquitinated, lipidated, acetylated and methylated proteins were prepd.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtVSmu7bO&md5=5d3d98ee85d9100e42a81035e65331be
  (b) Kent, S. B. H. Chem. Soc. Rev. 2009, 38, 338
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  6b
  Total chemical synthesis of proteins
  Kent, Stephen B. H.
  Chemical Society Reviews (2009), 38 (2), 338-351CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)
  A review. This tutorial review outlines the modern ligation methods that enable the efficient total chem. synthesis of enzymes and other protein mols. Key to this success is the chemoselective reaction of unprotected synthetic peptides ('chem. ligation'). Notably, native chem. ligation enables the reaction of two unprotected peptides in aq. soln. at neutral pH to form a single product in near quant. yield. Full-length synthetic polypeptides are folded to form the defined tertiary structure of the target protein mol., which is characterized by mass spectrometry, NMR, and x-ray crystallog., in addn. to biochem. and/or biol. activity.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXksVSntL8%253D&md5=ca6c6ab4e20f0e05d2b83b2fe1c19030
  (c) Hackenberger, C. P. R.; Schwarzer, D. Angew. Chem., Int. Ed. 2008, 47, 10030
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  6c
  Chemoselective ligation and modification strategies for peptides and proteins
  Hackenberger, Christian P. R.; Schwarzer, Dirk
  Angewandte Chemie, International Edition (2008), 47 (52), 10030-10074CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
  A review. The investigation of biol. processes by chem. methods, commonly referred to as chem. biol., often requires chem. access to biol. relevant macromols. such as peptides and proteins. Building upon solid-phase peptide synthesis, investigations have focused on the development of chemoselective ligation and modification strategies to link synthetic peptides or other functional units to larger synthetic and biol. relevant macromols. This review summarizes recent developments in the field of chemoselective ligation and modification strategies and illustrates their application, with examples ranging from the total synthesis of proteins to the semisynthesis of naturally modified proteins.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXislSitA%253D%253D&md5=7fc894096d44fb11c2c0187cc4fe79c7
7. 7
  Baslé, E.; Joubert, N.; Pucheault, M. Chem. Biol. 2010, 17, 213
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  7
  Protein Chemical Modification on Endogenous Amino Acids
  Basle, Emmanuel; Joubert, Nicolas; Pucheault, Mathieu
  Chemistry & Biology (Cambridge, MA, United States) (2010), 17 (3), 213-227CODEN: CBOLE2; ISSN:1074-5521. (Cell Press)
  A review. Chem. modification of protein is an arduous but fruitful task. Many chem. methods have been developed for such purpose by carefully balancing reactivity and selectivity. Now both chemists and biologists have in hand an arsenal of tools from which they can select a relevant reaction to tackle their problems. This review focuses on the various chem. transformations available for selective modification of proteins. It also provides a brief overview of some of their main applications, including detection of protein interactions, prepn. of bioconjugates, and protein microarrays.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXjvFKhurY%253D&md5=82a023a2f4e96136205bdb19901bd401
8. 8
  (a) Tasdelen, M. A.; Yagci, Y. Angew. Chem., Int. Ed. 2013, 52, 5930
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  8a
  Light-Induced Click Reactions
  Tasdelen, Mehmet Atilla; Yagci, Yusuf
  Angewandte Chemie, International Edition (2013), 52 (23), 5930-5938CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
  A review. Spatial and temporal control over chem. and biol. processes, both in terms of "tuning" products and providing site-specific control, is one of the most exciting and rapidly developing areas of modern science. For synthetic chemists, the challenge is to discover and develop selective and efficient reactions capable of generating useful mols. in a variety of matrixes. In recent studies, light has been recognized as a valuable method for detg. where, when, and to what extent a process is started or stopped. Accordingly, this Minireview will present the fundamental aspects of light-induced click reactions, highlight the applications of these reactions to diverse fields of study, and discuss the potential for this methodol. to be applied to the study of biomol. systems.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXntF2lsLY%253D&md5=19bac16930cc09dee72fcc1f0307befe
  (b) Palomo, J. M. Org. Biomol. Chem. 2012, 10, 9309
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  8b
  Click reactions in protein chemistry: from the preparation of semisynthetic enzymes to new click enzymes
  Palomo, Jose M.
  Organic & Biomolecular Chemistry (2012), 10 (47), 9309-9318CODEN: OBCRAK; ISSN:1477-0520. (Royal Society of Chemistry)
  A review. Click-chem. is an approach based on cycloaddn. reactions which has been successfully used as a chem. approach for complex org. mols. and which has recently starred in a boom in the world of protein chem. The advantage of the use of this technique in protein chem. is based on a very high and efficient chemoselectivity, which usually requires simple or no purifn. and is extremely rate-accelerated in aq. media. Here, the author discusses some of the most recent advances in the application of this reaction in selective enzyme surface modification for the creation of new semisynthetic enzymes (fluorescence labeled enzymes, peptide-enzyme conjugates, glycosylated enzymes), and interestingly, the recent design and creation of "click" enzymes.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xhs1yksL%252FO&md5=b50a62e468f8371886303df0c87bd04b
  (c) van Berkel, S. S.; van Eldijk, M. B.; van Hest, J. C. M. Angew. Chem., Int. Ed. 2011, 50, 8806
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  8c
  Staudinger Ligation as a Method for Bioconjugation
  van Berkel, Sander S.; van Eldijk, Mark B.; van Hest, Jan C. M.
  Angewandte Chemie, International Edition (2011), 50 (38), 8806-8827CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
  A review. In 1919 the German chemist Hermann Staudinger was the first to describe the reaction between an azide and a phosphine. It was not until recently, however, that Bertozzi and co-workers recognized the potential of this reaction as a method for bioconjugation and transformed it into the so-called Staudinger ligation. The bio-orthogonal character of both the azide and the phosphine functions resulted in the Staudinger ligation finding numerous applications in various complex biol. systems. For example, the Staudinger ligation has been used to label glycans, lipids, DNA, and proteins. Moreover, the Staudinger ligation has been used as a synthetic method to construct glycopeptides, microarrays, and functional biopolymers. In the emerging field of bio-orthogonal ligation strategies, the Staudinger ligation has set a high std. to which most of the new techniques are often compared. This review summarizes recent developments and new applications of the Staudinger ligation.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhtFWjsLrM&md5=dab931ed4005aeec679d5789fc778b0d
  (d) Lallana, E.; Riguera, R.; Fernandez-Megia, E. Angew. Chem., Int. Ed. 2011, 50, 8794
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  8d
  Reliable and Efficient Procedures for the Conjugation of Biomolecules through Huisgen Azide-Alkyne Cycloadditions
  Lallana, Enrique; Riguera, Ricardo; Fernandez-Megia, Eduardo
  Angewandte Chemie, International Edition (2011), 50 (38), 8794-8804CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
  A review. The CuI-catalyzed azide-alkyne cycloaddn. (CuAAC) has been established as a powerful coupling technol. for the conjugation of proteins, nucleic acids, and polysaccharides. Nevertheless, several shortcomings related to the presence of Cu, mainly oxidative degrdn. by reactive oxygen species and sample contamination by Cu, have been pointed out. This Minireview discusses key aspects found in the development of the efficient and benign functionalization of biomacromols. through CuAAC, as well as the Cu-free strain-promoted azide-alkyne cycloaddn. (SPAAC).
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhtVentbnF&md5=1c97cf8eb4e3dd99a31525ee4637f20b
9. 9
  (a) Villalonga, M. L.; Díez, P.; Sánchez, A.; Gamella, M.; Pingarrón, J. M.; Villalonga, R. Chem. Rev. 2014, 114, 4868
  [ ACS Full Text ], [ CAS], Google Scholar
  9a
  Neoglycoenzymes
  Villalonga, Maria L.; Diez, Paula; Sanchez, Alfredo; Gamella, Maria; Pingarron, Jose M.; Villalonga, Reynaldo
  Chemical Reviews (Washington, DC, United States) (2014), 114 (9), 4868-4917CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)
  A review. The rational design of proteins with desired functional properties by manipulation of their chem. compn. and three-dimensional structure is a challenge that has fascinated researchers in dierent disciplines during the last century. In this context, the ultimate goal of enzyme engineering has been to create novel and highly active enzymes with increased stability, selectivity, and substrate range, able to work in extreme physicochem. and biol. conditions. The coverage of this Review includes aspects concerning neoglycoenzyme synthesis, classification, structural and functional properties, and applications. For this purpose, reports ofoutstanding significance in neoglycoenzyme science will becritically discussed. A detailed description of the syntheticmethods used for prepg. protein glycoconjugates as well asthe properties and applications of these derivs. are beyond the scope of this Review and have been excellently covered in previous papers. Therefore, only the synthetic methods specifically adapted to enzyme artificial glycosylation will be discussed. This Review will highlight the new and/or improved properties showed by the artificial glycoenzymes as well as their most relevant applications. The predicted impact of neoglycoenzymes in new emerging research areas will be also encompassed.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhslygtro%253D&md5=b854da33b044abdaef75c0aaa75d2773
  (b) Wang, L.-X.; Amin, M. N. Chem. Biol. 2014, 21, 51
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  9b
  Chemical and Chemoenzymatic Synthesis of Glycoproteins for Deciphering Functions
  Wang, Lai-Xi; Amin, Mohammed N.
  Chemistry & Biology (Oxford, United Kingdom) (2014), 21 (1), 51-66CODEN: CBOLE2; ISSN:1074-5521. (Elsevier Ltd.)
  A review. Glycoproteins are an important class of biomols. involved in a no. of biol. recognition processes. However, natural and recombinant glycoproteins are usually produced as mixts. of glycoforms that differ in the structures of the pendent glycans, which are difficult to sep. in pure glycoforms. As a result, synthetic homogeneous glycopeptides and glycoproteins have become indispensable probes for detailed structural and functional studies. A no. of elegant chem. and biol. strategies have been developed for synthetic construction of tailor-made, full-size glycoproteins to address specific biol. problems. In this review, we highlight recent advances in chem. and chemoenzymic synthesis of homogeneous glycoproteins. Selected examples are given to demonstrate the applications of tailor-made, glycan-defined glycoproteins for deciphering glycosylation functions.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtF2htLk%253D&md5=da142c9aea24639867a2396b5fd17b9f
  (c) Schmaltz, R. M.; Hanson, S. R.; Wong, C.-H. Chem. Rev. 2011, 111, 4259
  [ ACS Full Text ], [ CAS], Google Scholar
  9c
  Enzymes in the Synthesis of Glycoconjugates
  Schmaltz, Ryan M.; Hanson, Sarah R.; Wong, Chi-Huey
  Chemical Reviews (Washington, DC, United States) (2011), 111 (7), 4259-4307CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)
  A review. This review is intended to update our previous discussion on the chemoenzymic synthesis of carbohydrates and glycoconjugates, with new emphasis placed on enzymic and whole-cell engineering techniques for the prodn. of homogeneous glycoproteins. Glycans, the carbohydrate portion of glycoconjugates, have diverse structures and far-reaching biol. functions that remain to be elucidated. The need to understand glycans and glycoconjugates has motivated an extraordinary amt. of work toward developing synthetic and chemoenzymic methods to produce them in a pure form over the past ten years. While many of these routes have been the subject of focused reviews, this account provides a thorough resource of the chemoenzymic and whole-cell tools that are available for producing glycans and glycoconjugates with defined structures. Because the covered topics are broad, succinct discussions of key concepts are provided in the text along with a few representative examples, while more in-depth consideration of subjects can be gained by consulting the extensive sources to the primary literature provided throughout.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXosFymtbY%253D&md5=e5c2ef236283d58da086afe5ea571818
  (d) Gamblin, D. P.; Scanlan, E. M.; Davis, B. G. Chem. Rev. 2009, 109, 131
  [ ACS Full Text ], [ CAS], Google Scholar
  9d
  Glycoprotein Synthesis: An Update
  Gamblin, David P.; Scanlan, Eoin M.; Davis, Benjamin G.
  Chemical Reviews (Washington, DC, United States) (2009), 109 (1), 131-163CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)
  A review. The developments in glycoprotein synthesis since 2002 are highlighted in this review. Topics of discussion are biol. importance of glycopeptide/glycoproteins, glycopeptide assembly and assembly strategies, chem. and enzymic methods for glycoprotein synthesis, mol. and cell biol. techniques in biosynthesis methods. This work includes strategies for synthesizing proteins as clin. biopharmaceuticals in the near future.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXhsFals7rI&md5=0bce8ff0722b4c57380bc12718255b33
10. 10
  Nischan, N.; Hackenberger, C. P. R. J. Org. Chem. 2014, 79, 10727
  [ ACS Full Text ], [ CAS], Google Scholar
  10
  Site-specific PEGylation of Proteins: Recent Developments
  Nischan, Nicole; Hackenberger, Christian P. R.
  Journal of Organic Chemistry (2014), 79 (22), 10727-10733CODEN: JOCEAH; ISSN:0022-3263. (American Chemical Society)
  A review. The attachment of linear polyethylene glycol (PEG) to peptides and proteins for their stabilization for in vivo applications is a milestone in pharmaceutical research and protein-drug development. However, conventional methods often lead to heterogeneous PEGylation mixts. with reduced protein activity. Current synthetic efforts aim to provide site-specific approaches by chemoselective targeting of canonical and noncanonical amino acids and to improve the PEG architecture. This synopsis highlights recent work in this area, which also resulted in improved pharmacokinetics of peptide and protein therapeutics.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhslOksr%252FJ&md5=7241ca75ef24af2dd0bffca520c4f6ea
11. 11
  (a) Matyjaszewski, K.; Tsarevsky, N. V. J. Am. Chem. Soc. 2014, 136, 6513
  [ ACS Full Text ], [ CAS], Google Scholar
  11a
  Macromolecular Engineering by Atom Transfer Radical Polymerization
  Matyjaszewski, Krzysztof; Tsarevsky, Nicolay V.
  Journal of the American Chemical Society (2014), 136 (18), 6513-6533CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  A review. This Perspective presents recent advances in macromol. engineering enabled by ATRP. They include the fundamental mechanistic and synthetic features of ATRP with emphasis on various catalytic/initiation systems that use parts-per-million concns. of Cu catalysts and can be run in environmentally friendly media, e.g., water. The roles of the major components of ATRP-monomers, initiators, catalysts, and various additives-are explained, and their reactivity and structure are correlated. The effects of media and external stimuli on polymn. rates and control are presented. Some examples of precisely controlled elements of macromol. architecture, such as chain uniformity, compn., topol., and functionality, are discussed. Syntheses of polymers with complex architecture, various hybrids, and bioconjugates are illustrated. Examples of current and forthcoming applications of ATRP are covered. Future challenges and perspectives for macromol. engineering by ATRP are discussed.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXmslSrurY%253D&md5=a9277a80a8ad824041cdd4b19559d4cb
  (b) Wallat, J. D.; Rose, K. A.; Pokorski, J. K. Polym. Chem. 2014, 5, 1545
  [ Crossref], [ CAS], Google Scholar
  11b
  Proteins as substrates for controlled radical polymerization
  Wallat, Jaqueline D.; Rose, Katie A.; Pokorski, Jonathan K.
  Polymer Chemistry (2014), 5 (5), 1545-1558CODEN: PCOHC2; ISSN:1759-9962. (Royal Society of Chemistry)
  A review. This review describes fundamental contributions in the area of proteins as macroinitiators and macro-chain transfer agents (CTA) for controlled radical polymn. (CRP). The review specifically highlights the concept of 'grafting-from' proteins, as new and efficient chem. has been developed to polymerize directly from protein substrates in aq. media. As the past ten years have shown, CRP has proven a powerful tool in the functionalization of proteins. This review considers the methods used to install protein based initiators and CTAs, the principle examples of ATRP and RAFT as polymn. methods, and finishes with more advanced methodologies such as the combination of genetic modifications and polymer chem., proteins as nanoparticles for drug delivery, and unnatural amino acid initiators.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhvFGhs78%253D&md5=89867bb09e64a24e5f2b5cb8fe8f7ae3
12. 12
  (a) King, M.; Wagner, A. Bioconjugate Chem. 2014, 25, 825
  [ ACS Full Text ], [ CAS], Google Scholar
  12a
  Developments in the Field of Bioorthogonal Bond Forming Reactions-Past and Present Trends
  King, Mathias; Wagner, Alain
  Bioconjugate Chemistry (2014), 25 (5), 825-839CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
  A review. In response to the ever increasing need of chem. biol. for new tools, a wide variety of new, highly selective reactions have been described. Herein we report a summary of recent developments and the historical background on bioorthogonal ligation reactions.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXmt1Gjsbs%253D&md5=c71e8c5fa752acc8c1285af1f18c60f7
  (b) Lang, K.; Chin, J. W. Chem. Rev. 2014, 114, 4764
  [ ACS Full Text ], [ CAS], Google Scholar
  12b
  Cellular Incorporation of Unnatural Amino Acids and Bioorthogonal Labeling of Proteins
  Lang, Kathrin; Chin, Jason W.
  Chemical Reviews (Washington, DC, United States) (2014), 114 (9), 4764-4806CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)
  A review. A range of bioorthogonal reactions are described and methods discussed include the cellular cotranslational incorporation of unnatural amino acids bearing bioorthogonal functionalities into proteins via residue-specific or site-specific approaches. Applications of residue-specific incorporation and labeling and developments of site-specific incorporation and labeling are outlined.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXkslamtrY%253D&md5=bbb5b3099d3fccf801262e6b0d51676b
  (c) Patterson, D. M.; Nazarova, L. A.; Prescher, J. A. ACS Chem. Biol. 2014, 9, 592
  [ ACS Full Text ], [ CAS], Google Scholar
  12c
  Finding the Right (Bioorthogonal) Chemistry
  Patterson, David M.; Nazarova, Lidia A.; Prescher, Jennifer A.
  ACS Chemical Biology (2014), 9 (3), 592-605CODEN: ACBCCT; ISSN:1554-8929. (American Chemical Society)
  A review. Bioorthogonal chemistries can be used to tag diverse classes of biomols. in cells and other complex environments. With over 20 unique transformations now available, though, selecting an appropriate reaction for a given expt. is challenging. The authors compare and contrast the most common classes of bioorthogonal chemistries and provide a framework for matching the reactions with downstream applications. The authors also discuss ongoing efforts to identify novel biocompatible reactions and methods to control their reactivity. The continued expansion of the bioorthogonal toolkit will provide new insights into biomol. networks and functions and thus refine the authors' understanding of living systems.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXpt1Ohtg%253D%253D&md5=d65dabc417be90fa15af42e97cbd0422
  (d) Lang, K.; Chin, J. W. ACS Chem. Biol. 2014, 9, 16
  [ ACS Full Text ], [ CAS], Google Scholar
  12d
  Bioorthogonal Reactions for Labeling Proteins
  Lang, Kathrin; Chin, Jason W.
  ACS Chemical Biology (2014), 9 (1), 16-20CODEN: ACBCCT; ISSN:1554-8929. (American Chemical Society)
  A review. Bioorthogonal reactions for labeling proteins in vitro, on the cell surface and inside living cells are discussed. Some of the reactions discussed include Staudinger ligations, alkyne-azide cycloaddn., metal-catalyzed reactions, aminothiol condensations, light-induced dipolar cycloaddn. reaction and Diels-Alder reactions.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXmsVShuw%253D%253D&md5=62049f6d20016cfa62c4ad34d63dcec6
  (e) Takaoka, Y.; Ojida, A.; Hamachi, I. Angew. Chem., Int. Ed. 2013, 52, 4088
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  12e
  Protein Organic Chemistry and Applications for Labeling and Engineering in Live-Cell Systems
  Takaoka, Yousuke; Ojida, Akio; Hamachi, Itaru
  Angewandte Chemie, International Edition (2013), 52 (15), 4088-4106CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
  A review. The modification of proteins with synthetic probes is a powerful means of elucidating and engineering the functions of proteins both in vitro and in live cells or in vivo. Herein the authors review recent progress in chem.-based protein modification methods and their application in protein engineering, with particular emphasis on the following four strategies: (1) the bioconjugation reactions of amino acids on the surfaces of natural proteins, mainly applied in test-tube settings; (2) the bioorthogonal reactions of proteins with non-natural functional groups; (3) the coupling of recognition and reactive sites using an enzyme or short peptide tag-probe pair for labeling natural amino acids; and (4) ligand-directed labeling chemistries for the selective labeling of endogenous proteins in living systems. Overall, these techniques represent a useful set of tools for application in chem. biol., with the methods 2-4 in particular being applicable to crude (living) habitats. Although still in its infancy, the use of org. chem. for the manipulation of endogenous proteins, with subsequent applications in living systems, represents a worthy challenge for many chemists.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXivVKhsLY%253D&md5=9f7ef6846cc3e64f802254bd25d25941
  (f) Debets, M. F.; van Hest, J. C. M.; Rutjes, F. P. J. T. Org. Biomol. Chem. 2013, 11, 6439
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  12f
  Bioorthogonal labelling of biomolecules: new functional handles and ligation methods
  Debets, Marjoke F.; van Hest, Jan C. M.; Rutjes, Floris P. J. T.
  Organic & Biomolecular Chemistry (2013), 11 (38), 6439-6455CODEN: OBCRAK; ISSN:1477-0520. (Royal Society of Chemistry)
  This review provides a literature overview of bioorthogonal ligation methods for protein modification, which have largely evolved over the last 15 years. Since 1990, various new reactions have been developed that do not involve naturally occurring functional handles. Esp. the development of such so-called bioorthogonal ligations has significantly contributed to our ability to selectively modify biomols. not only in the test tube, but also in living systems.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhsVCjtL7I&md5=61856d4d5fe81c40a1657f1f23c1aff7
  (g) Ramil, C. P.; Lin, Q. Chem. Commun. 2013, 49, 11007
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  12g
  Bioorthogonal chemistry: strategies and recent developments
  Ramil, Carlo P.; Lin, Qing
  Chemical Communications (Cambridge, United Kingdom) (2013), 49 (94), 11007-11022CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
  A review. The use of covalent chem. to track biomols. in their native environment-a focus of bioorthogonal chem.-has received considerable interest recently among chem. biologists and org. chemists alike. To facilitate wider adoption of bioorthogonal chem. in biomedical research, a central effort in the last few years has been focused on the optimization of a few known bioorthogonal reactions, particularly with respect to reaction kinetics improvement, novel genetic encoding systems, and fluorogenic reactions for bioimaging. During these optimizations, three strategies have emerged, including the use of ring strain for substrate activation in the cycloaddn. reactions, the discovery of new ligands and privileged substrates for accelerated metal-catalyzed reactions, and the design of substrates with pre-fluorophore structures for rapid "turn-on" fluorescence after selective bioorthogonal reactions. In addn., new bioorthogonal reactions based on either modified or completely unprecedented reactant pairs have been reported. Finally, increasing attention has been directed toward the development of mutually exclusive bioorthogonal reactions and their applications in multiple labeling of a biomol. in cell culture. In this feature article, the authors wish to present the recent progress in bioorthogonal reactions through the selected examples that highlight the above-mentioned strategies. Considering increasing sophistication in bioorthogonal chem. development, the authors strive to project several exciting opportunities where bioorthogonal chem. can make a unique contribution to biol. in the near future.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhslWls7vL&md5=55e8bcb626cf7d28ea9937a8fe800ca8
  (h) Sletten, E. M.; Bertozzi, C. R. Angew. Chem., Int. Ed. 2009, 48, 6974
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  12h
  Bioorthogonal Chemistry: Fishing for Selectivity in a Sea of Functionality
  Sletten, Ellen M.; Bertozzi, Carolyn R.
  Angewandte Chemie, International Edition (2009), 48 (38), 6974-6998CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
  A review. The study of biomols. in their native environments is a challenging task because of the vast complexity of cellular systems. Technologies developed in the last few years for the selective modification of biol. species in living systems have yielded new insights into cellular processes. Key to these new techniques are bioorthogonal chem. reactions, whose components must react rapidly and selectively with each other under physiol. conditions in the presence of the plethora of functionality necessary to sustain life. Herein the authors describe the bioorthogonal chem. reactions developed to date and how they can be used to study biomols.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXhtV2ltrvK&md5=993199cb4deabc186848bae6fe81f605
  (i) Shih, H.-W.; Kamber, D. N.; Prescher, J. A. Curr. Opin. Chem. Biol. 2014, 21, 103
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  12i
  Building better bioorthogonal reactions
  Shih, Hui-Wen; Kamber, David N.; Prescher, Jennifer A.
  Current Opinion in Chemical Biology (2014), 21 (), 103-111CODEN: COCBF4; ISSN:1367-5931. (Elsevier B.V.)
  A review. Over the past two decades, there has been intense interest in designing and implementing selective (bioorthogonal) reactions for biomol. tracking. Here we review the most widely used bioorthogonal chemistries in live cells and animals, drawing particular attention to the unique functional groups underlying these transformations. We also describe recent efforts to tune functional group reactivities and stabilities to access even more rapid and selective chemistries. Last, we highlight ongoing challenges in identifying new bioorthogonal reagents and combinations of reactions that can be used concurrently to tag multiple biomols.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtleis7vK&md5=f74ddb8b84c289deb9b1985add394dbb
  (j) McKay, C. S.; Finn, M. G. Chem. Biol. 2014, 21, 1075
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  12j
  Click Chemistry in Complex Mixtures: Bioorthogonal Bioconjugation
  McKay, Craig S.; Finn, M. G.
  Chemistry & Biology (Oxford, United Kingdom) (2014), 21 (9), 1075-1101CODEN: CBOLE2; ISSN:1074-5521. (Elsevier Ltd.)
  A review. The selective chem. modification of biol. mols. drives a good portion of modern drug development and fundamental biol. research. While a few early examples of reactions that engage amine and thiol groups on proteins helped establish the value of such processes, the development of reactions that avoid most biol. mols. so as to achieve selectivity in desired bond-forming events has revolutionized the field. We provide an update on recent developments in bioorthogonal chem. that highlights key advances in reaction rates, biocompatibility, and applications. While not exhaustive, we hope this summary allows the reader to appreciate the rich continuing development of good chem. that operates in the biol. setting.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsFyrur7N&md5=64a6e5ea8a232b97fce61d1268093fe4
  (k) Spicer, C. D.; Davis, B. G. Nat. Commun. 2014, 5, 4740
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  12k
  Selective chemical protein modification
  Spicer, Christopher D.; Davis, Benjamin G.
  Nature Communications (2014), 5 (), 4740CODEN: NCAOBW; ISSN:2041-1723. (Nature Publishing Group)
  The chem. modification of proteins is an important tool for probing natural systems and synthesizing novel conjugates. Here, Spicer and Davis review the merits and limitations of the most useful methods for selective modification at both natural and unnatural amino acids.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXksVeksb4%253D&md5=055c882ff0405b0bbb91edca3bcef8cb
13. 13
  Chalker, J. M.; Bernardes, G. J. L.; Lin, Y. A.; Davis, B. G. Chem.—Asian J. 2009, 4, 630
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  13
  Chemical modification of proteins at cysteine: opportunities in chemistry and biology
  Chalker, Justin M.; Bernardes, Goncalo J. L.; Lin, Yuya A.; Davis, Benjamin G.
  Chemistry - An Asian Journal (2009), 4 (5), 630-640CODEN: CAAJBI; ISSN:1861-4728. (Wiley-VCH Verlag GmbH & Co. KGaA)
  A review. Chem. modification of proteins is a rapidly expanding area in chem. biol. Selective installation of biochem. probes has led to a better understanding of natural protein modification and macromol. function. In other cases such chem. alterations have changed the protein function entirely. Addnl., tethering therapeutic cargo to proteins has proven invaluable in campaigns against disease. For controlled, selective access to such modified proteins, a unique chem. handle is required. Cysteine, with its unique reactivity, has long been used for such modifications. Cysteine has enjoyed wide-spread use in selective protein modification, yet new applications and even new reactions continue to emerge. This Focus Review highlights the enduring utility of cysteine in protein modification with special focus on recent innovations in chem. and biol. assocd. with such modifications.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXmvVaisLk%253D&md5=ff4c5cc1590ec98c0f22f168a9320fcd
14. 14
  Hemantha, H. P.; Bavikar, S. N.; Herman-Bachinsky, Y.; Haj-Yahya, N.; Bondalapati, S.; Ciechanover, A.; Brik, A. J. Am. Chem. Soc. 2014, 136, 2665
  [ ACS Full Text ], [ CAS], Google Scholar
  14
  Nonenzymatic Polyubiquitination of Expressed Proteins
  Hemantha, Hosahalli P.; Bavikar, Sudhir N.; Herman-Bachinsky, Yifat; Haj-Yahya, Najat; Bondalapati, Somasekhar; Ciechanover, Aaron; Brik, Ashraf
  Journal of the American Chemical Society (2014), 136 (6), 2665-2673CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  Ubiquitination is one of the most ubiquitous posttranslational modifications in eukaryotes and is involved in various cellular events such as proteasomal degrdn. and DNA repair. The overwhelming majority of studies aiming to understand ubiquitination and deubiquitination have employed unanchored ubiquitin chains and mono-ubiquitinated proteins. To shed light on these processes at the mol. level, it is crucial to have facile access to ubiquitin chains linked to protein substrates. Such conjugates are highly difficult to prep. homogenously and in workable quantities using the enzymic machinery. To address this formidable challenge we developed new chem. approaches to covalently attach ubiquitin chains to a protein substrate through its Cys residue. A key aspect of this approach is the installation of acyl hydrazide functionality at the C-terminus of the proximal Ub, which allows, after ubiquitin chain assembly, the introduction of various reactive electrophiles for protein conjugation. Employing α-globin as a model substrate, we demonstrate the facile conjugation to K48-linked ubiquitin chains, bearing up to four ubiquitins, through disulfide and thioether linkages. These bioconjugates were examd. for their behavior with the USP2 enzyme, which was found to cleave the ubiquitin chain in a similar manner to unanchored ones. Furthermore, proteasomal degrdn. study showed that di-ubiquitinated α-globin is rapidly degraded in contrast to the mono-ubiquitinated counterpart, highlighting the importance of the chain lengths on proteasomal degrdn. The present work opens unprecedented opportunities in studying the ubiquitin signal by enabling access to site-specifically polyubiquitinated proteins with an increased size and complexity.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXpslKjtg%253D%253D&md5=7a8a3abf522f486dd23c46a966b1c21a
15. 15
  (a) Massa, S.; Xavier, C.; De Vos, J.; Caveliers, V.; Lahoutte, T.; Muyldermans, S.; Devoogdt, N. Bioconjugate Chem. 2014, 25, 979
  [ ACS Full Text ], [ CAS], Google Scholar
  15a
  Site-Specific Labeling of Cysteine-Tagged Camelid Single-Domain Antibody-Fragments for Use in Molecular Imaging
  Massa, Sam; Xavier, Catarina; De Vos, Jens; Caveliers, Vicky; Lahoutte, Tony; Muyldermans, Serge; Devoogdt, Nick
  Bioconjugate Chemistry (2014), 25 (5), 979-988CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
  Site-specific labeling of mol. imaging probes allows the development of a homogeneous tracer population. The resulting batch-to-batch reproducible pharmacokinetic and pharmacodynamic properties are of great importance for clin. translation. Camelid single-domain antibody-fragments (sdAbs)-the recombinantly produced antigen-binding domains of heavy-chain antibodies, also called Nanobodies-are proficient probes for mol. imaging. To safeguard their intrinsically high binding specificity and affinity and to ensure the tracer's homogeneity, we developed a generic strategy for the site-specific labeling of sdAbs via a thio-ether bond. The unpaired cysteine was introduced at the carboxyl-terminal end of the sdAb to eliminate the risk of antigen binding interference. The spontaneous dimerization and capping of the unpaired cysteine required a redn. step prior to conjugation. This was optimized with the mild reducing agent 2-mercaptoethylamine in order to preserve the domain's stability. As a proof-of-concept the reduced probe was subsequently conjugated to maleimide-DTPA, for labeling with indium-111. A single conjugated tracer was obtained and confirmed via mass spectrometry. The specificity and affinity of the new sdAb-based imaging probe was validated in a mouse xenograft tumor model using a modified clin. lead compd. targeting the human epidermal growth factor receptor 2 (HER2) cancer biomarker. These data provide a versatile and standardized strategy for the site-specific labeling of sdAbs. The conjugation to the unpaired cysteine results in the prodn. of a homogeneous group of tracers and is a multimodal alternative to the technetium-99m labeling of sdAbs.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXmslOqsr0%253D&md5=ea61ec2fd78ba6096f3097272ade36e9
  (b) Morales-Sanfrutos, J.; Lopez-Jaramillo, J.; Ortega-Munoz, M.; Megia-Fernandez, A.; Perez-Balderas, F.; Hernandez-Mateo, F.; Santoyo-Gonzalez, F. Org. Biomol. Chem. 2010, 8, 667
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  15b
  Vinyl sulfone: a versatile function for simple bioconjugation and immobilization
  Morales-Sanfrutos, Julia; Lopez-Jaramillo, Javier; Ortega-Munoz, Mariano; Megia-Fernandez, Alicia; Perez-Balderas, Francisco; Hernandez-Mateo, Fernando; Santoyo-Gonzalez, Francisco
  Organic & Biomolecular Chemistry (2010), 8 (3), 667-675CODEN: OBCRAK; ISSN:1477-0520. (Royal Society of Chemistry)
  The authors report here on the capabilities of the vinyl sulfone function for the covalent coupling of proteins to detection labels, other biomols. and solid supports by exploiting the Michael-type addn. of this function to the amine-contg. residues, in conditions that preserve the functionality and biol. integrity of those biol. macromols. The easy functionalization of tags and solid supports with the vinyl sulfone function is a valuable tool in omic sciences that allows their coupling with the amine and thiol groups present in the proteogenic residues of proteins, in mild and green conditions compatible with their biol. function.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXnsV2qtg%253D%253D&md5=398fa4786531ec2eb89794476bda4012
  (c) Morales-Sanfrutos, J.; Lopez-Jaramillo, F. J.; Hernandez-Mateo, F.; Santoyo-Gonzalez, F. J. Org. Chem. 2010, 75, 4039
  [ ACS Full Text ], [ CAS], Google Scholar
  15c
  Vinyl Sulfone Bifunctional Tag Reagents for Single-Point Modification of Proteins
  Morales-Sanfrutos, Julia; Lopez-Jaramillo, Francisco Javier; Hernandez-Mateo, Fernando; Santoyo-Gonzalez, Francisco
  Journal of Organic Chemistry (2010), 75 (12), 4039-4047CODEN: JOCEAH; ISSN:0022-3263. (American Chemical Society)
  The introduction of multiple labels onto biomols. is a challenge. The authors report herein the synthesis of vinyl sulfone derivatized bifunctional tag single-attachment-point reagents (BTSAP) bearing biotin and a fluorescent tag and their applications in proteins for the introduction of multiple labels by the Michael-type addn. of the electrophilic vinyl sulfone group. These BTSAP reagents were easily synthesized by a two-step chem. strategy involving the prepn. of alkyne vinyl sulfone derivatized tags (AVST) and subsequent click CuAAC attachment of a second azide functionalized tag. The direct coupling of BTSAP reagents with the low reactive protein horseradish peroxidase (HRP) turned it into a dual reporter group (i.e., fluorescence and peroxidase activity) that may be coupled to any recognition system via biotin-avidin affinity. The AVST compds. are not mere synthetic intermediates for the prepn. of BTSAP reagents but valuable clickable self-reporting compds. that allow the simultaneous introduction in proteins of an alkyne function and labeling when conjugated via the vinyl sulfone group. The implementation of these clickable AVST compds. in a CuAAC-based sequential approach also allows attainment of the dual labeling of HRP. This approach yields equiv. results in terms of fluorescent labeling, specific activity, and functionality of the biotin tag when compared with the direct bifunctional labeling by the BTSAP reagent. However, for life science this direct approach is more convenient since it avoids the use of copper catalysis, overcoming the toxicity drawback of this metal in biol. systems.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXmsVGjtLc%253D&md5=f2e96b4e9528959fec044d12a4b92b0d
16. 16
  Cal, P. M. S. D.; Bernardes, G. J. L.; Gois, P. M. P. Angew. Chem., Int. Ed. 2014, 53, 10585
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  16
  Cysteine-Selective Reactions for Antibody Conjugation
  Cal, Pedro M. S. D.; Bernardes, Goncalo J. L.; Gois, Pedro M. P.
  Angewandte Chemie, International Edition (2014), 53 (40), 10585-10587CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
  A review. The unique targeting ability of antibodies has triggered burgeoning interest in the attachment of potent cytotoxic drugs onto these biomols. to create antibody-drug conjugates (ADCs). A key factor in the design of therapeutically useful ADCs is the ability to create chem. defined, stable protein-drug conjugates. The aim of this highlight is to discuss new methods for site-selective bioconjugation at native or engineered cysteines, methods which may be used to build homogeneous and stable ADCs.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXht1ams7jF&md5=a9b477a09aa18c06fa325db95184e436
17. 17
  Badescu, G.; Bryant, P.; Swierkosz, J.; Khayrzad, F.; Pawlisz, E.; Farys, M.; Cong, Y.; Muroni, M.; Rumpf, N.; Brocchini, S.; Godwin, A. Bioconjugate Chem. 2013, 25, 460
  [ ACS Full Text ], Google Scholar
  There is no corresponding record for this reference.
18. 18
  (a) Bailey, J. J.; Bundle, D. R. Org. Biomol. Chem. 2014, 12, 2193
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  18a
  Synthesis of high-mannose 1-thio glycans and their conjugation to protein
  Bailey, Justin J.; Bundle, David R.
  Organic & Biomolecular Chemistry (2014), 12 (14), 2193-2213CODEN: OBCRAK; ISSN:1477-0520. (Royal Society of Chemistry)
  The oligosaccharides Man4 and Man5, substructures of the high-mannose glycans of HIV glycoprotein gp120, were synthesized with a terminal 1-thiomannopyranose residue. The anomeric thiol can be readily converted to an azidomethyl aglycon through reaction with dichloromethane and displacement with sodium azide. The resulting oligomannans were then conjugated to ubiquitin utilizing thiol alkylation or azide/alkyne reactive tethers of minimal length. By combining high efficiency conjugation reactions and a short tether, we sought to establish conjugation conditions that would permit high d. clustering of oligomannans in conjugate vaccines that could produce antibodies able to bind gp120 and potentially neutralize virus. LC-UV-MS was used to sep., identify and quantify the ubiquitin glycoconjugates with differing degrees of oligomannan incorporation. Binding of the HIV protective monoclonal antibody 2G12 and Con A to microtitre plates coated with glycoconjugates was measured by ELISA.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXktF2mtb0%253D&md5=1f8db49f9e037175bb8efbff1d0075b0
  (b) Wurm, F. R.; Klok, H.-A. Chem. Soc. Rev. 2013, 42, 8220
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  18b
  Be squared: expanding the horizon of squaric acid-mediated conjugations
  Wurm, Frederik R.; Klok, Harm-Anton
  Chemical Society Reviews (2013), 42 (21), 8220-8236CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)
  A review. Squaric acid diesters can be applied as reagents to couple two amino-functional compds. Consecutive coupling of two amines allows the synthesis of asym. squaric acid bisamides with either low mol. wt. compds. but also biomols. or polymers. The key feature of the squaric acid diester mediated coupling is the reduced reactivity of the resulting ester-amide after the first amidation step of the diester. This allows the sequential amidation and generation of asym. squaramides with high selectivity and in high yields. This article gives an overview of the well-established squaric acid diester mediated coupling reactions for glycoconjugates and presents recent advances that aim to expand this very versatile reaction protocol to the modification of peptides and proteins.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhsFOitrzJ&md5=456989efee4f9e7fc6ff08d9ac44e11f
  (c) Patel, M. K.; Vijayakrishnan, B.; Koeppe, J. R.; Chalker, J. M.; Doores, K. J.; Davis, B. G. Chem. Commun. 2010, 46, 9119
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  18c
  Analysis of the dispersity in carbohydrate loading of synthetic glycoproteins using MALDI-TOF mass spectrometry
  Patel, Mitul K.; Vijayakrishnan, Balakumar; Koeppe, Julia R.; Chalker, Justin M.; Doores, Katie J.; Davis, Benjamin G.
  Chemical Communications (Cambridge, United Kingdom) (2010), 46 (48), 9119-9121CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
  Statistical correlation of mass spectrum peak broadening with product dispersity in protein conjugation reactions allows more detailed characterization of putative therapeutic conjugates.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhsVynurbN&md5=831ffe2c13f1d8f7a9fc2be3478a41f6
  (d) Liu, Z.; Liu, T.; Lin, Q.; Bao, C.; Zhu, L. Chem. Commun. 2014, 50, 1256
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  18d
  Photoreleasable thiol chemistry for facile and efficient bioconjugation
  Liu, Zhenzhen; Liu, Tao; Lin, Qiuning; Bao, Chunyan; Zhu, Linyong
  Chemical Communications (Cambridge, United Kingdom) (2014), 50 (10), 1256-1258CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
  A facile methodol. for light-triggered release of thiols under mild conditions is presented, which can be utilized for in situ bioconjugation with protein and quantum dot nanoparticles (QDs) efficiently.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXjtVWltg%253D%253D&md5=e293bbc7ba5261c3aa4f781b29127eea
19. 19
  Asano, S.; Patterson, J. T.; Gaj, T.; Barbas, C. F. Angew. Chem., Int. Ed. 2014, 53, 11783
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  19
  Site-selective labeling of a lysine residue in human serum albumin
  Asano, Shigehiro; Patterson, James T.; Gaj, Thomas; Barbas, Carlos F., III
  Angewandte Chemie, International Edition (2014), 53 (44), 11783-11786CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
  Conjugation to human serum albumin (HSA) has emerged as a powerful approach for extending the in vivo half-life of many small mol. and peptide/protein drugs. Current HSA conjugation strategies, however, can often yield heterogeneous mixts. with inadequate pharmacokinetics, low efficacies, and variable safety profiles. Here, we designed and synthesized analogs of TAK-242, a small mol. inhibitor of Toll-like receptor 4, that primarily reacted with a single lysine residue of HSA. These TAK-242-based cyclohexene compds. demonstrated robust reactivity, and Lys64 was identified as the primary conjugation site. A bivalent HSA conjugate was also prepd. in a site-specific manner. Addnl., HSA-cyclohexene conjugates maintained higher levels of stability both in human plasma and in mice than the corresponding maleimide conjugates. This new conjugation strategy promises to broadly enhance the performance of HSA conjugates for numerous applications.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsV2ntrfO&md5=e5dee953030a7fb53e28f3b88915a852
20. 20
  Adamo, R.; Nilo, A.; Castagner, B.; Boutureira, O.; Berti, F.; Bernardes, G. J. L. Chem. Sci. 2013, 4, 2995
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  20
  Synthetically defined glycoprotein vaccines: current status and future directions
  Adamo, Roberto; Nilo, Alberto; Castagner, Bastien; Boutureira, Omar; Berti, Francesco; Bernardes, Goncalo J. L.
  Chemical Science (2013), 4 (8), 2995-3008CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)
  A review. Primary examples in vaccine design have shown good levels of carbohydrate-specific antibody generation when raised using extd. or fully synthetic capsular polysaccharide glycans covalently coupled to a protein carrier. Herein, the authors cover recent clin. developments of carbohydrate-based vaccines and describe how novel cutting-edge methodol. for the total synthesis of oligosaccharides and for the precise placement of carbohydrates at pre-detd. sites within a protein may be used to further improve the safety and efficacy of glycovaccines.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtVehs7jN&md5=eb09336f0a6302efb364de7539fd94a4
21. 21
  Crotti, S.; Zhai, H.; Zhou, J.; Allan, M.; Proietti, D.; Pansegrau, W.; Hu, Q.-Y.; Berti, F.; Adamo, R. ChemBioChem 2014, 15, 836
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  21
  Defined Conjugation of Glycans to the Lysines of CRM197 Guided by their Reactivity Mapping
  Crotti, Stefano; Zhai, Huili; Zhou, Jing; Allan, Martin; Proietti, Daniela; Pansegrau, Werner; Hu, Qi-Ying; Berti, Francesco; Adamo, Roberto
  ChemBioChem (2014), 15 (6), 836-843CODEN: CBCHFX; ISSN:1439-4227. (Wiley-VCH Verlag GmbH & Co. KGaA)
  Systematic characterization of the reactivity of the lysine moieties in CRM197 towards N-hydroxysuccinimide linkers bearing alkynes or azides is described. This involves two-step conjugation of various glycans to CRM197 by click chem. in a well-defined manner. By semiquant. LC-MS/MS anal. of proteolytic digests of the conjugates formed, the reactivity of lysine residues in the protein was mapped and ranked. Computational anal. of the solvent accessibility of each lysine residue (based on the CRM197 crystal structure) established a correlation between reactivity and surface exposure. By this approach, conjugation involving lysine residues (normally a random process) can be controlled. It enables the prepn. of lysine-mediated glycoconjugates with improved batch-to-batch reproducibility, thereby producing neo-glycoconjugates with more-consistent biol. activity.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXjvVyrurk%253D&md5=2c5f51f81d507458a45b6467fda0c519
22. 22
  Chen, X.; Muthoosamy, K.; Pfisterer, A.; Neumann, B.; Weil, T. Bioconjugate Chem. 2012, 23, 500
  [ ACS Full Text ], [ CAS], Google Scholar
  22
  Site-Selective Lysine Modification of Native Proteins and Peptides via Kinetically Controlled Labeling
  Chen, Xi; Muthoosamy, Kasturi; Pfisterer, Anne; Neumann, Boris; Weil, Tanja
  Bioconjugate Chemistry (2012), 23 (3), 500-508CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
  The site-selective modification of the proteins RNase A, lysozyme C, and the peptide hormone somatostatin is presented via a kinetically controlled labeling approach. A single lysine residue on the surface of these biomols. reacts with an activated biotinylation reagent at mild conditions, physiol. pH, and at RT in a high yield of over 90%. In addn., fast reaction speed, quick and easy purifn., as well as low reaction temps. are particularly attractive for labeling sensitive peptides and proteins. Furthermore, the multifunctional bioorthogonal bioconjugation reagent (I) has been achieved allowing the site-selective incorporation of a single ethynyl group. The introduced ethynyl group is accessible for, e.g., click chem. as demonstrated by the reaction of RNase A with azidocoumarin. The approach reported herein is fast, less labor-intensive and minimizes the risk for protein misfolding. Kinetically controlled labeling offers a high potential for addressing a broad range of native proteins and peptides in a site-selective fashion and complements the portfolio of recombinant techniques or chemoenzymic approaches.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XitlOlt78%253D&md5=829098df917ba084086466464e585ae5
23. 23
  del Castillo, T.; Morales-Sanfrutos, J.; Santoyo-González, F.; Magez, S.; Lopez-Jaramillo, F. J.; Garcia-Salcedo, J. A. ChemMedChem 2014, 9, 383
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  23
  Monovinyl Sulfone β-Cyclodextrin. A Flexible Drug Carrier System
  del Castillo, Teresa; Marales-Sanfrutos, Julia; Santoyo-Gonzalez, Francisco; Magez, Stefan; Lopez-Jaramillo, F. Javier; Garcia-Salcedo, Jose A.
  ChemMedChem (2014), 9 (2), 383-389CODEN: CHEMGX; ISSN:1860-7179. (Wiley-VCH Verlag GmbH & Co. KGaA)
  Cyclodextrins have been conjugated to target various receptors and have also been functionalized with carbohydrates for targeting specific organs. However, this approach is based on a rigid design that implies the ad hoc synthesis of each cyclodextrin-targeting agent conjugate. We hypothesized that: 1) a modular design that decouples the carrier function from the targeting function leads to a flexible system, 2) combining the reactivity of the vinyl sulfone group toward biomols. that act as targeting agents with the ability of cyclodextrin to form complexes with a wide range of drugs may yield a versatile system that allows the targeting of different organs with different drugs, and 3) the higher reactivity of histidine residues toward the vinyl sulfone group can be exploited to couple the cyclodextrin to the targeting system with a degree of regioselectivity. As a proof of concept, we synthesized a monovinyl sulfone β-cyclodextrin (module responsible for the payload), which, after coupling to recombinant antibody fragments raised against Trypanosoma brucei (module responsible for targeting) and loading with nitrofurazone (module responsible for therapeutic action) resulted in an effective delivery system that targets the surface of the parasites and shows trypanocidal activity.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhvFarsbvE&md5=82ebab64bd2d107e31bab214b4b543ec
24. 24
  Díaz-Rodríguez, A.; Davis, B. G. Curr. Opin. Chem. Biol. 2011, 15, 211
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  24
  Chemical modification in the creation of novel biocatalysts
  Diaz-Rodriguez, Alba; Davis, Benjamin G.
  Current Opinion in Chemical Biology (2011), 15 (2), 211-219CODEN: COCBF4; ISSN:1367-5931. (Elsevier B.V.)
  A review. Enzymes are able to perform a multitude of chem. and biochem. transformations with efficiencies that are typically unrivaled by chem. catalysts. However, these evolved systems may lack breadth or utility in other non-natural applications. Altering enzyme and protein scaffolds through covalent modification can expand the usefulness of native biocatalysts not only for synthetic applications but also for therapeutic use. This review summarizes recent developments in the field of chem. modification of enzymes and how they can be applied to synthesis and biol. research.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXksFKnt70%253D&md5=330369b050ac09259dbe567b542b19b1
25. 25
  McGrath, N. A.; Andersen, K. A.; Davis, A. K. F.; Lomax, J. E.; Raines, R. T. Chem. Sci. 2015, 6, 752
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  25
  Diazo compounds for the bioreversible esterification of proteins
  McGrath, Nicholas A.; Andersen, Kristen A.; Davis, Amy K. F.; Lomax, Jo E.; Raines, Ronald T.
  Chemical Science (2015), 6 (1), 752-755CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)
  A diazo compd. is shown to convert carboxylic acids to esters efficiently in an aq. environment. The basicity of the diazo compd. is crit.: low basicity does not lead to a reaction but high basicity leads to hydrolysis. This reactivity extends to carboxylic acid groups in a protein. The ensuing esters are hydrolyzed by human cellular esterases to regenerate protein carboxyl groups. This new mode of chem. modification could enable the key advantages of prodrugs to be translated from small-mols. to proteins.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhs1KnsL%252FM&md5=46fa03b7c0cdefd4a921117476799d17
26. 26
  (a) Kramer, J. R.; Deming, T. J. Biomacromolecules 2012, 13, 1719
  [ ACS Full Text ], [ CAS], Google Scholar
  26a
  Preparation of Multifunctional and Multireactive Polypeptides via Methionine Alkylation
  Kramer, Jessica R.; Deming, Timothy J.
  Biomacromolecules (2012), 13 (6), 1719-1723CODEN: BOMAF6; ISSN:1525-7797. (American Chemical Society)
  We report the development of a new "click"-type reaction for polypeptide modification based on the chemoselective alkylation of thioether groups in methionine residues. The controlled synthesis of methionine polymers and their alkylation by a broad range of functional reagents to yield stable sulfonium derivs. are described. These "methionine click" functionalizations are compatible with deprotection of other functional groups, use an inexpensive, natural amino acid that is readily polymd. and requires no protecting groups, and allow the introduction of a diverse range of functionality and reactive groups onto polypeptides.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XnsFOnsLw%253D&md5=952433a60f87eab5b8282739c587cf92
  (b) Kramer, J. R.; Deming, T. J. Chem. Commun. 2013, 49, 5144
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  26b
  Reversible chemoselective tagging and functionalization of methionine containing peptides
  Kramer, Jessica R.; Deming, Timothy J.
  Chemical Communications (Cambridge, United Kingdom) (2013), 49 (45), 5144-5146CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
  Reagents were developed to allow chemoselective tagging of methionine residues in peptides and polypeptides, subsequent bioorthogonal functionalization of the tags, and cleavage of the tags when desired. This methodol. can be used for triggered release of therapeutic peptides, or release of tagged protein digests from affinity columns.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXnsFarur0%253D&md5=5428bf5090a00b0e5667fec156c3ec5d
27. 27
  Tanaka, K.; Fukase, K.; Katsumura, S. Synlett 2011, 2011, 2115
  [ Crossref], Google Scholar
  There is no corresponding record for this reference.
28. 28
  Robinson, M. A.; Charlton, S. T.; Garnier, P.; Wang, X.-T.; Davis, S. S.; Perkins, A. C.; Frier, M.; Duncan, R.; Savage, T. J.; Wyatt, D. A.; Watson, S. A.; Davis, B. G. Proc. Natl. Acad. Sci. U. S. A. 2004, 101, 14527
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  28
  LEAPT: Lectin-directed enzyme-activated prodrug therapy
  Robinson, Mark A.; Charlton, Stuart T.; Garnier, Philippe; Wang, Xiang-tao; Davis, Stanley S.; Perkins, Alan C.; Frier, Malcolm; Duncan, Ruth; Savage, Tony J.; Wyatt, David A.; Watson, Susan A.; Davis, Benjamin G.
  Proceedings of the National Academy of Sciences of the United States of America (2004), 101 (40), 14527-14532CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)
  Targeted drug delivery to selected sites allows reduced toxicity, enhanced efficiency and interchangeable target potential. We describe a bipartite drug-delivery system that exploits (i) endogenous carbohydrate-to-lectin binding to localize glycosylated enzyme conjugates to specific, predetd. cell types followed by (ii) administration of a prodrug activated by that predelivered enzyme at the desired site. The carbohydrate structure of an α-L-rhamnopyranosidase enzyme was specifically engineered through enzymic deglycosylation and chem. reglycosylation. Combined in vivo and in vitro techniques (gamma scintigraphy, microautoradiog. and confocal microscopy) detd. organ and cellular localization and demonstrated successful activation of α-L-rhamnopyranoside prodrug. Ligand competition expts. revealed enhanced, specific localization by endocytosis and a strongly carbohydrate-dependent, 60-fold increase in selectivity toward target cell hepatocytes that generated a >30-fold increase (from 0.02 to 0.66 mg) in protein delivered. Furthermore, glycosylation engineering enhanced the serum-uptake rate and enzyme stability. This created enzyme activity (0.2 units in hepatocytes) for prodrug therapy, the target of which was switched simply by sugar-type alteration. The therapeutic effectiveness of lectin-directed enzyme-activated prodrug therapy was shown through the construction of the prodrug of doxorubicin, Rha-DOX, and its application to reduce tumor burden in a hepatocellular carcinoma (HepG2) disease model.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXovVeru70%253D&md5=4d402206223fd1056fcde67391290c4d
29. 29
  Bavaro, T.; Filice, M.; Temporini, C.; Tengattini, S.; Serra, I.; Morelli, C. F.; Massolini, G.; Terreni, M. RSC Adv. 2014, 4, 56455
  [ Crossref], [ CAS], Google Scholar
  29
  Chemoenzymatic synthesis of neoglycoproteins driven by the assessment of protein surface reactivity
  Bavaro, T.; Filice, M.; Temporini, C.; Tengattini, S.; Serra, I.; Morelli, C. F.; Massolini, G.; Terreni, M.
  RSC Advances (2014), 4 (99), 56455-56465CODEN: RSCACL; ISSN:2046-2069. (Royal Society of Chemistry)
  In this paper a series of 2-iminomethoxyethyl mannose-based mono- and disaccharides have been synthesized by a chemoenzymic approach and used in coupling reactions with ε-amino groups of lysine residues in a model protein (RNase A, RNase A) to give semisynthetic neoglycoconjugates. In order to study the influence of structure of the glycans on the conjugation outcomes, an accurate characterization of the prepd. neoglycoproteins was performed by a combination of ESI-MS and LC-MS anal. methods. The analyses of the chymotryptic digests of the all neoglycoconjugates revealed six Lys-glycosylation sites with a the following order of lysine reactivity: Lys 1 » Lys 91 ≃ Lys 31 > Lys 61 ≃ Lys 66. A computational anal. of the reactivity of each lysine residue has been also carried out considering several parameters (amino acids surface exposure and pKa, protein flexibility). The in silico evaluation seems to confirm the order in lysine reactivity resulting from proteomic anal.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsl2gu7fE&md5=71e23551d12e603ca87faf2bfdcb21ba
30. 30
  Cal, P. M. S. D.; Vicente, J. B.; Pires, E.; Coelho, A. V.; Veiros, L. F.; Cordeiro, C.; Gois, P. M. P. J. Am. Chem. Soc. 2012, 134, 10299
  [ ACS Full Text ], [ CAS], Google Scholar
  30
  Iminoboronates: A new strategy for reversible protein modification
  Cal, Pedro M. S. D.; Vicente, Joao B.; Pires, Elisabete; Coelho, Ana V.; Veiros, Luis F.; Cordeiro, Carlos; Gois, Pedro M. P.
  Journal of the American Chemical Society (2012), 134 (24), 10299-10305CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  Protein modification has entered the limelight of chem. and biol. sciences, since, by appending small mols. into proteins surfaces, fundamental biol. and biophys. processes may be studied and even modulated in a physiol. context. Herein the authors present a new strategy to modify the lysine's ε-amino group and the protein's N-terminal, based on the formation of stable iminoboronates in aq. media. This functionality enables the stable and complete modification of these amine groups, which can be reversible upon the addn. of fructose, dopamine, or glutathione. A detailed DFT study is also presented to rationalize the obsd. stability toward hydrolysis of the iminoboronate constructs.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XnsF2gurY%253D&md5=ad8e9263660d93401e1ccad61cd312db
31. 31
  Cal, P. M. S. D.; Frade, R. F. M.; Chudasama, V.; Cordeiro, C.; Caddick, S.; Gois, P. M. P. Chem. Commun. 2014, 50, 5261
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  31
  Targeting cancer cells with folic acid-iminoboronate fluorescent conjugates
  Cal, Pedro M. S. D.; Frade, Raquel F. M.; Chudasama, Vijay; Cordeiro, Carlos; Caddick, Stephen; Gois, Pedro M. P.
  Chemical Communications (Cambridge, United Kingdom) (2014), 50 (40), 5261-5263CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
  Herein we present the synthesis of fluorescent 2-acetylbenzeneboronic acids that undergo B-N promoted conjugation with lysozyme and N-(2-aminoethyl) folic acid (EDA-FA), generating conjugates that are selectively recognized and internalized by cancer cells that over-express folic acid receptors.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXmsFequ7Y%253D&md5=dbd13397a6d6d33283e118e55ffb244c
32. 32
  Diethelm, S.; Schafroth, M. A.; Carreira, E. M. Org. Lett. 2014, 16, 3908
  [ ACS Full Text ], [ CAS], Google Scholar
  32
  Amine-Selective Bioconjugation Using Arene Diazonium Salts
  Diethelm, Stefan; Schafroth, Michael A.; Carreira, Erick M.
  Organic Letters (2014), 16 (15), 3908-3911CODEN: ORLEF7; ISSN:1523-7052. (American Chemical Society)
  A novel bioconjugation strategy is presented that relies on the coupling of diazonium terephthalates with amines in proteins. The diazonium captures the amine while the vicinal ester locks it through cyclization, ensuring no reversibility. The reaction is highly efficient and proceeds under mild conditions and short reaction times. Densely functionalized, complex natural products were directly coupled to proteins using low concns. of coupling partners.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtFCrtbfF&md5=91876c83f67d31189c501b567630900e
33. 33
  Chan, A. O.-Y.; Ho, C.-M.; Chong, H.-C.; Leung, Y.-C.; Huang, J.-S.; Wong, M.-K.; Che, C.-M. J. Am. Chem. Soc. 2012, 134, 2589
  [ ACS Full Text ], [ CAS], Google Scholar
  33
  Modification of N-Terminal α-Amino Groups of Peptides and Proteins Using Ketenes
  Chan, Anna On-Yee; Ho, Chi-Ming; Chong, Hiu-Chi; Leung, Yun-Chung; Huang, Jie-Sheng; Wong, Man-Kin; Che, Chi-Ming
  Journal of the American Chemical Society (2012), 134 (5), 2589-2598CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  A method of highly selective N-terminal modification of proteins as well as peptides by an isolated ketene was developed. Modification of a library of unprotected peptides XSKFR (X varies over 20 natural amino acids) by an alkyne-functionalized ketene (I) at room temp. at pH 6.3 resulted in excellent N-terminal selectivity (modified α-amino group/modified ε-amino group = >99:1) for 13 out of the 20 peptides and moderate-to-high N-terminal selectivity (4:1 to 48:1) for 6 of the 7 remaining peptides. Using an alkyne-functionalized N-hydroxysuccinimide (NHS) ester (II) instead of I, the modification of peptides XSKFR gave internal lysine-modified peptides for 5 out of the 20 peptides and moderate-to-low N-terminal selectivity (5:1 to 1:4) for 13 out of the 20 peptides. Proteins including insulin, lysozyme, RNase A, and a therapeutic protein BCArg were selectively N-terminally modified at room temp. using ketene I, in contrast to the formation of significant or major amts. of di-, tri-, or tetra-modified proteins in the modification by NHS ester II. The I-modified proteins were further functionalized by a dansyl azide compd. through click chem. without the need for prior treatment.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhsVWisbg%253D&md5=af037a958d63180265aba0762ca77af7
34. 34
  (a) Kulkarni, C.; Kinzer-Ursem, T. L.; Tirrell, D. A. ChemBioChem 2013, 14, 1958
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  34a
  Selective Functionalization of the Protein N Terminus with N-Myristoyl Transferase for Bioconjugation in Cell Lysate
  Kulkarni, Chethana; Kinzer-Ursem, Tamara L.; Tirrell, David A.
  ChemBioChem (2013), 14 (15), 1958-1962CODEN: CBCHFX; ISSN:1439-4227. (Wiley-VCH Verlag GmbH & Co. KGaA)
  This article describes the selective functionalization of the protein N terminus with N-myristoyl transferase for bioconjugation in cell lysate. NMT selectively labels engineered, non-natural substrate proteins in bacteria with a reactive, non-natural fatty acid. Quant. NMT-mediated labeling of engineered substrate proteins with reactive Myr analogs, as well as rapid and robust surface capture of labeled proteins to produce protein microarrays directly from cell lysate were reported.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhsVeisL7N&md5=ce54089c128b282c217a6b7330ad9338
  (b) Wagner, A. M.; Fegley, M. W.; Warner, J. B.; Grindley, C. L. J.; Marotta, N. P.; Petersson, E. J. J. Am. Chem. Soc. 2011, 133, 15139
  [ ACS Full Text ], [ CAS], Google Scholar
  34b
  N-Terminal Protein Modification Using Simple Aminoacyl Transferase Substrates
  Wagner, Anne M.; Fegley, Mark W.; Warner, John B.; Grindley, Christina L. J.; Marotta, Nicholas P.; Petersson, E. James
  Journal of the American Chemical Society (2011), 133 (38), 15139-15147CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  Methods for synthetically manipulating protein structure enable greater flexibility in the study of protein function. Previous characterization of the Escherichia coli aminoacyl tRNA transferase (AaT) has shown that it can modify the N-terminus of a protein with an amino acid from a tRNA or a synthetic oligonucleotide donor. Here, it is demonstrated that AaT can efficiently use a minimal adenosine substrate, which can be synthesized in one to two steps from readily available starting materials. The enzymic activity of AaT was characterized with aminoacyl adenosyl donors and it was found that reaction products do not inhibit AaT. The use of adenosyl donors removes the substrate limitations imposed by the use of synthetases for tRNA charging and avoids the complex synthesis of an oligonucleotide donor. Thus, these AaT donors increase the potential substrate scope and reaction scale for N-terminal protein modification under conditions that maintain folding.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhtFaks7rI&md5=09ad42b27993fa2817c220962c17fb1a
35. 35
  (a) Schlick, T. L.; Ding, Z.; Kovacs, E. W.; Francis, M. B. J. Am. Chem. Soc. 2005, 127, 3718
  [ ACS Full Text ], [ CAS], Google Scholar
  35a
  Dual-surface modification of the Tobacco mosaic virus
  Schlick, Tara L.; Ding, Zhebo; Kovacs, Ernest W.; Francis, Matthew B.
  Journal of the American Chemical Society (2005), 127 (11), 3718-3723CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  The protein shell of the tobacco mosaic virus (TMV) provides a robust and practical tubelike scaffold for the prepn. of nanoscale materials. To expand the range of applications for which the capsid can be used, two synthetic strategies have been developed for the attachment of new functionality to either the exterior or the interior surface of the virus. The first of these is accomplished using a highly efficient diazonium coupling/oxime formation sequence, which installs >2000 copies of a material component on the capsid exterior. Alternatively, the inner cavity of the tube can be modified by attaching amines to glutamic acid side chains through a carbodiimide coupling reaction. Both of these reactions have been demonstrated for a series of substrates, including biotin, chromophores, and crown ethers. Through the attachment of PEG polymers to the capsid exterior, org.-sol. TMV rods have been prepd. Finally, the orthogonality of these reactions has been demonstrated by installing different functional groups on the exterior and interior surfaces of the same capsid assemblies.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXhs1ant7w%253D&md5=417dfb81edc43b89ef121f8c67ed653a
  (b) Hooker, J. M.; Kovacs, E. W.; Francis, M. B. J. Am. Chem. Soc. 2004, 126, 3718
  [ ACS Full Text ], [ CAS], Google Scholar
  35b
  Interior surface modification of bacteriophage MS2
  Hooker, Jacob M.; Kovacs, Ernest W.; Francis, Matthew B.
  Journal of the American Chemical Society (2004), 126 (12), 3718-3719CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  An efficient strategy for the interior surface functionalization of MS2 viral capsids is reported, featuring a new hetero-Diels-Alder bioconjugation reaction. After virus isolation, the RNA genome was removed from the spherical particles by exposure to pH 11.8 conditions for a period of 4 h. Following this, 180 tyrosine residues on the interior surface of each "empty" capsid shell were modified by using a site-selective diazonium-coupling reaction. To attach addnl. functionality, the azo conjugate was reduced with Na2S2O4 to afford an ortho-amino tyrosine deriv. Oxidn. of this moiety with NaIO4 produced an o-iminoquinone on the protein surface, which was found to undergo an efficient hetero-Diels-Alder reaction with N-(4-aminophenyl)acrylamide. This 4-step procedure can be carried out in under 4 h, reaches high levels of conversion, and yields the desired conjugates in >60% overall yield.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXhvVyqu7o%253D&md5=278140e9122ec58334673c6415d3ed1b
36. 36
  Gavrilyuk, J.; Ban, H.; Nagano, M.; Hakamata, W.; Barbas, C. F. Bioconjugate Chem. 2012, 23, 2321
  [ ACS Full Text ], [ CAS], Google Scholar
  36
  Formylbenzene Diazonium Hexafluorophosphate Reagent for Tyrosine-Selective Modification of Proteins and the Introduction of a Bioorthogonal Aldehyde
  Gavrilyuk, Julia; Ban, Hitoshi; Nagano, Masanobu; Hakamata, Wataru; Barbas, Carlos F.
  Bioconjugate Chemistry (2012), 23 (12), 2321-2328CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
  4-Formylbenzene diazonium hexafluorophosphate (FBDP) is a novel bench-stable cryst. diazonium salt that reacts selectively with tyrosine to install a bioorthogonal aldehyde functionality. Model studies with N-acyl-tyrosine methylamide allowed the authors to identify conditions optimal for tyrosine ligation reactions with small peptides and proteins. FBDP-based conjugation was used for the facile introduction of small mol. tags, poly(ethylene glycol) chains (PEGylation), and functional small mols. onto model proteins and to label the surface of living cells.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xhslemu7vP&md5=65b3af53d0d71681ded8c108ba2054aa
37. 37
  Zhang, J.; Ma, D.; Du, D.; Xi, Z.; Yi, L. Org. Biomol. Chem. 2014, 12, 9528
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  37
  An efficient reagent for covalent introduction of alkynes into proteins
  Zhang, Jie; Ma, Dejun; Du, Dawei; Xi, Zhen; Yi, Long
  Organic & Biomolecular Chemistry (2014), 12 (47), 9528-9531CODEN: OBCRAK; ISSN:1477-0520. (Royal Society of Chemistry)
  A cheap and bench-stable reagent was synthesized for direct and covalent introduction of alkynes into tyrosine of target proteins, which can be further modified based on Click reaction to achieve fluorescence labeling or PEGylation. This reagent should be a generally useful toolbox for chem. biol. and biomaterials.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhslKrsbrL&md5=9b70cd50737258a4898f180fa6f9a4b0
38. 38
  Chen, S.; Tsao, M.-L. Bioconjugate Chem. 2013, 24, 1645
  [ ACS Full Text ], [ CAS], Google Scholar
  38
  Genetic Incorporation of a 2-Naphthol Group into Proteins for Site-Specific Azo Coupling
  Chen, Shuo; Tsao, Meng-Lin
  Bioconjugate Chemistry (2013), 24 (10), 1645-1649CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
  The 2-naphthol analog of tyrosine, 2-amino-3-(6-hydroxy-2-naphthyl)-propanoic acid (NpOH), has been genetically introduced into proteins in Escherichia coli. This is achieved through the directed evolution of orthogonal aminoacyl-tRNA synthetase/tRNA pairs that selectively charge the target amino acid in response to the amber stop codon, UAG. Moreover, chemoselective azo coupling reactions have been revealed between the 2-naphthol group and diazotized aniline derivs. that are substituted with an electron donating moiety. The coupling reactions required a very mild condition (pH 7) with great reaction rate (less than 2 h at 0 °C), high efficiency, and excellent selectivity.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhsFehu7zE&md5=a0f72083e99920da221eddbf7bff198f
39. 39
  (a) Lorenzi, M.; Puppo, C.; Lebrun, R.; Lignon, S.; Roubaud, V.; Martinho, M.; Mileo, E.; Tordo, P.; Marque, S. R. A.; Gontero, B.; Guigliarelli, B.; Belle, V. Angew. Chem., Int. Ed. 2011, 50, 9108
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  39a
  Tyrosine-Targeted Spin Labeling and EPR Spectroscopy: An Alternative Strategy for Studying Structural Transitions in Proteins
  Lorenzi, Magali; Puppo, Carine; Lebrun, Regine; Lignon, Sabrina; Roubaud, Valerie; Martinho, Marlene; Mileo, Elisabetta; Tordo, Paul; Marque, Sylvain R. A.; Gontero, Brigitte; Guigliarelli, Bruno; Belle, Valerie
  Angewandte Chemie, International Edition (2011), 50 (39), 9108-9111, S9108/1-S9108/9CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
  The authors present the selective grafting of a nitroxide probe to tyrosine by using, the Mannich-type reaction on CP12, a protein bearing only one natural tyrosine residue. This unique tyrosine residue, located at position 78 in the sequence of a total of 80 amino acids, makes this protein an ideal candidate for demonstrating the feasibility of tyrosine-targeted spin labeling.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhtVOmsrjE&md5=5495a295b0609aa25af8d2b900f1aeab
  (b) McFarland, J. M.; Joshi, N. S.; Francis, M. B. J. Am. Chem. Soc. 2008, 130, 7639
  [ ACS Full Text ], [ CAS], Google Scholar
  39b
  Characterization of a Three-Component Coupling Reaction on Proteins by Isotopic Labeling and Nuclear Magnetic Resonance Spectroscopy
  McFarland, Jesse M.; Joshi, Neel S.; Francis, Matthew B.
  Journal of the American Chemical Society (2008), 130 (24), 7639-7644CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  A three-component Mannich-type electrophilic arom. substitution reaction was previously developed to target the phenolic side chain of tyrosine residues on proteins. This reaction proceeds under mild conditions and provides a convenient alternative to lysine-targeting strategies. However, the use of reactive aldehydes, such as formaldehyde, warrants careful inspection of the reaction products to ensure that other modifications have not occurred. Through the use of isotopically enriched reagents, NMR-based studies were used to obtain structural confirmation of the tyrosine-modification products. These expts. also revealed the formation of a reaction byproduct arising from the indole ring of tryptophan residues. Cysteine residues were shown to not participate in the reaction, except in the case of a reduced disulfide, which formed a dithioacetal. The authors anticipate that this anal. method will prove useful for the detailed study of a no. of bioconjugation reactions.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXmtlWnur8%253D&md5=bb7ca7ed789e3e447e7de7dac5c54941
  (c) Romanini, D. W.; Francis, M. B. Bioconjugate Chem. 2008, 19, 153
  [ ACS Full Text ], [ CAS], Google Scholar
  39c
  Attachment of Peptide Building Blocks to Proteins Through Tyrosine Bioconjugation
  Romanini, Dante W.; Francis, Matthew B.
  Bioconjugate Chemistry (2008), 19 (1), 153-157CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
  Recent efforts have yielded a no. of short peptide sequences with useful binding, sensing, and cellular uptake properties. To attach these sequences to tyrosine residues on intact proteins, a three-component Mannich-type strategy is reported. Two solid phase synthetic routes were developed to access peptides up to 20 residues in length with anilines at either the N- or C-termini. In the presence of 20 mM formaldehyde, these functional groups were coupled to tyrosine residues on proteins under mild reaction conditions. The identities of the resulting bioconjugates were confirmed using mass spectrometry and immunoblot anal. Screening expts. have demonstrated that the method is compatible with substrates contg. all of the amino acids, including lysine and cysteine residues. Importantly, tyrosine residues on proteins exhibit much faster reaction rates, allowing short peptides contg. this residue to be coupled without cross reactions.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXhsVWgtbbF&md5=e66a855c3a122ae3ea53db9e7d0c9be3
  (d) Joshi, N. S.; Whitaker, L. R.; Francis, M. B. J. Am. Chem. Soc. 2004, 126, 15942
  [ ACS Full Text ], [ CAS], Google Scholar
  39d
  A Three-Component Mannich-Type Reaction for Selective Tyrosine Bioconjugation
  Joshi, Neel S.; Whitaker, Leanna R.; Francis, Matthew B.
  Journal of the American Chemical Society (2004), 126 (49), 15942-15943CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  A new selective bioconjugation reaction is described for the modification of tyrosine residues on protein substrates. The reaction uses imines formed in situ from aldehydes and electron-rich anilines to modify phenolic side chains through a Mannich-type electrophilic arom. substitution pathway. The reaction takes place under mild pH and temp. conditions and can modify protein substrates at concns. as low as 20 μM. Using an efficient fluorescence-based assay, we demonstrated the reaction using a no. of aldehydes and protein targets. Importantly, proteins lacking surface-accessible tyrosines remained unmodified. It was also demonstrated that enzymic activity is preserved under the mild reaction conditions. This strategy represents one of the first carbon-carbon bond-forming reactions for protein modification and provides an important complement to more commonly used lysine- and cysteine-based methods.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXpvFWjur8%253D&md5=d9cb096caf0ad9046b42c8e6bdb7145a
40. 40
  Mileo, E.; Etienne, E.; Martinho, M.; Lebrun, R.; Roubaud, V.; Tordo, P.; Gontero, B.; Guigliarelli, B.; Marque, S. R. A.; Belle, V. Bioconjugate Chem. 2013, 24, 1110
  [ ACS Full Text ], [ CAS], Google Scholar
  40
  Enlarging the Panoply of Site-Directed Spin Labeling Electron Paramagnetic Resonance (SDSL-EPR): Sensitive and Selective Spin-Labeling of Tyrosine Using an Isoindoline-Based Nitroxide
  Mileo, Elisabetta; Etienne, Emilien; Martinho, Marlene; Lebrun, Regine; Roubaud, Valerie; Tordo, Paul; Gontero, Brigitte; Guigliarelli, Bruno; Marque, Sylvain R. A.; Belle, Valerie
  Bioconjugate Chemistry (2013), 24 (6), 1110-1117CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
  Site-directed spin labeling (SDSL) combined with EPR spectroscopy has emerged as a powerful approach to study structure and dynamics in proteins. One limitation of this approach is the fact that classical spin labels are functionalized to be grafted on natural or site-directed mutagenesis generated cysteine residues. Despite the widespread success of cysteine-based modification strategies, the technique becomes unsuitable when cysteine residues play a functional or structural role in the protein under study. To overcome this limitation, the authors propose an isoindoline-based nitroxide to selectively target tyrosine residues using a Mannich type reaction, the feasibility of which has been demonstrated in a previous study. This nitroxide has been synthesized and successfully grafted successively on p-cresol, a small tetrapeptide and a model protein: a small chloroplastic protein CP12 having functional cysteines and a single tyrosine. Studying the assocn. of the labeled CP12 with its partner protein, the isoindoline-based nitroxide is a good reporter to reveal changes in its local environment contrary to the previous study where the label was poorly sensitive to probe structural changes. The successful targeting of tyrosine residues with the isoindoline-based nitroxide thus offers a highly promising approach, complementary to the classical cysteine-SDSL one, which significantly enlarges the field of applications of the technique for probing protein dynamics.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXmvFyqs7s%253D&md5=c6e154a7f0c42f5dad4b167afb3c371a
41. 41
  Guo, H.-M.; Minakawa, M.; Ueno, L.; Tanaka, F. Bioorg. Med. Chem. Lett. 2009, 19, 1210
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  41
  Synthesis and evaluation of a cyclic imine derivative conjugated to a fluorescent molecule for labeling of proteins
  Guo, Hai-Ming; Minakawa, Maki; Ueno, Lynn; Tanaka, Fujie
  Bioorganic & Medicinal Chemistry Letters (2009), 19 (4), 1210-1213CODEN: BMCLE8; ISSN:0960-894X. (Elsevier B.V.)
  A cyclic imine conjugated to a fluorescent dansyl group was synthesized and used for covalent labeling of proteins. The covalent attachment to proteins was confirmed by gel electrophoresis and mass anal.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXit1Wrurw%253D&md5=89f3027f9c158ec07d41199bed05b0ed
42. 42
  Ban, H.; Gavrilyuk, J.; Barbas, C. F. J. Am. Chem. Soc. 2010, 132, 1523
  [ ACS Full Text ], [ CAS], Google Scholar
  42
  Tyrosine bioconjugation through aqueous ene-type reactions: A click-like reaction for tyrosine
  Ban, Hitoshi; Gavrilyuk, Julia; Barbas, Carlos F.
  Journal of the American Chemical Society (2010), 132 (5), 1523-1525CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  A new and versatile class of cyclic diazodicarboxamides that reacts efficiently and selectively with phenols and the phenolic side chain of tyrosine through an ene-like reaction is reported. This mild aq. tyrosine ligation reaction works over a broad pH range and expands the repertoire of aq. chemistries available for small mol., peptide, and protein modification. The tyrosine ligation reactions are shown to be compatible with the labeling of native enzymes and antibodies in a buffered aq. soln. This reaction provides a novel synthetic approach to bispecific antibodies. The authors believe this reaction will find broad utility in peptide and protein chem. and in the chem. of phenol-contg. compds.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXkt1Wrug%253D%253D&md5=876ee34e149ceed4f70f7fd4efbb25ba
43. 43
  (a) Hu, Q.-Y.; Allan, M.; Adamo, R.; Quinn, D.; Zhai, H.; Wu, G.; Clark, K.; Zhou, J.; Ortiz, S.; Wang, B.; Danieli, E.; Crotti, S.; Tontini, M.; Brogioni, G.; Berti, F. Chem. Sci. 2013, 4, 3827
  [ Crossref], [ CAS], Google Scholar
  43a
  Synthesis of a well-defined glycoconjugate vaccine by a tyrosine-selective conjugation strategy
  Hu, Qi-Ying; Allan, Martin; Adamo, Roberto; Quinn, Doug; Zhai, Huili; Wu, Guangxiang; Clark, Kirk; Zhou, Jing; Ortiz, Sonia; Wang, Bing; Danieli, Elisa; Crotti, Stefano; Tontini, Marta; Brogioni, Giulia; Berti, Francesco
  Chemical Science (2013), 4 (10), 3827-3832CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)
  An anti-candidiasis glycoconjugate vaccine was prepd. via a tyrosine-selective alkynylation and a click chem. mediated glycoconjugation sequence. It features a well-defined glycan, protein carrier, and connectivity. The construct, although with significantly lower carbohydrate loading and a shorter β-(1,3) glucan chain than the well-established anti-candidiasis vaccine derived from the random conjugation of laminarin at lysines, elicited a comparable level of specific IgG antibodies.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtlentrnP&md5=ff8226bd1851cd36db4d672ac93edf39
  (b) Adamo, R.; Hu, Q.-Y.; Torosantucci, A.; Crotti, S.; Brogioni, G.; Allan, M.; Chiani, P.; Bromuro, C.; Quinn, D.; Tontini, M.; Berti, F. Chem. Sci. 2014, 5, 4302
  [ Crossref], [ CAS], Google Scholar
  43b
  Deciphering the structure-immunogenicity relationship of anti-Candida glycoconjugate vaccines
  Adamo, Roberto; Hu, Qi-Ying; Torosantucci, Antonella; Crotti, Stefano; Brogioni, Giulia; Allan, Martin; Chiani, Paola; Bromuro, Carla; Quinn, Douglas; Tontini, Marta; Berti, Francesco
  Chemical Science (2014), 5 (11), 4302-4311CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)
  The elucidation of the mol. details underlying the immune properties of glycoconjugate vaccines has largely focused on the carbohydrate moiety, while very little is known on the effect of the corresponding conjugation sites. Herein we constructed a set of β-(1 → 3) glucan oligosaccharide conjugates with a well-defined glycan structure, connected to patterns of predetd. tyrosine or lysine residues onto the CRM197 carrier protein. To evaluate the effect of multivalent architecture in the glycan presentation, a novel linker enabling tyrosine-directed ligation of couples of oligosaccharides was prepd. The potential of these constructs as anti-Candida vaccines was evaluated in vivo, using as controls glycoconjugates prepd. by a conventional random coupling strategy, and the structure-immune properties relationship was established. We found that: (i) the tyrosine-directed ligation resulted in higher anti-glycan IgG levels in comparison to the conjugation at predetd. lysine residues; (ii) the presentation of the carbohydrate antigen with a biantennary cluster of glycans onto specific tyrosine residues did not further increase the anti-glycan antibody level; (iii) the sera deriving from immunization with defined conjugates at tyrosine and, particularly at lysine residues, were proven stronger inhibitors of fungal adhesion to human epithelial cells in comparison to those from conjugates prepd. by classic random chem.; (iv) the presence of antibodies directed to the linkers did not affect the anti-glycan immune response. These findings suggest that a careful choice of the defined sites of conjugation and the loading d. of antigens are important factors to raise high-quality anti-carbohydrate antibodies.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtFSgs7fF&md5=6c6469c55d8a2020eb7ad1d424f78525
  (c) Nilo, A.; Allan, M.; Brogioni, B.; Proietti, D.; Cattaneo, V.; Crotti, S.; Sokup, S.; Zhai, H.; Margarit, I.; Berti, F.; Hu, Q.-Y.; Adamo, R. Bioconjugate Chem. 2014, 25, 2105
  [ ACS Full Text ], [ CAS], Google Scholar
  43c
  Tyrosine-Directed Conjugation of Large Glycans to Proteins via Copper-Free Click Chemistry
  Nilo, Alberto; Allan, Martin; Brogioni, Barbara; Proietti, Daniela; Cattaneo, Vittorio; Crotti, Stefano; Sokup, Samantha; Zhai, Huili; Margarit, Immaculada; Berti, Francesco; Hu, Qi-Ying; Adamo, Roberto
  Bioconjugate Chemistry (2014), 25 (12), 2105-2111CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
  The insertion of alkyne-contg. bifunctional linkers into the tyrosine residues of the carrier protein, followed by the copper mediated azide-alkyne [3 + 2] cycloaddn. of carbohydrates, is a robust approach for the prepn. of glycoconjugates with defined glycans, carrier, and connectivity. Conjugation of Group B Streptococcus (GBS) capsular polysaccharides to streptococcal pilus protein could extend the vaccine coverage to a variety of strains. Application of the authors' protocol to these large charged polysaccharides occurred at low yields. Herein the authors developed a tyrosine-directed conjugation approach based on the copper-free click chem. of sugars modified with cyclooctynes, which enables efficient condensation of synthetic carbohydrates. Most importantly, this strategy is more effective than the corresponding copper catalyzed reaction for the insertion of GBS onto the tyrosine residues of GBS pilus proteins, previously selected as vaccine antigens through the so-called reverse vaccinol. Integrity of protein epitopes in the modified proteins was ascertained by competitive ELISA, and conjugation of polysaccharide to protein was confirmed by SDS page electrophoresis and immunoblot assays. The amt. of conjugated polysaccharide was estd. by high-performance anion-exchange chromatog. coupled with pulsed amperometric detection (HPAEC-PAD). The described technol. is particularly suitable for proteins used with the dual role of vaccine antigen and carrier for the carbohydrate haptens.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhvFGku7zI&md5=7e62afdb0e1d506b664dc101af627c9c
44. 44
  Bauer, D. M.; Ahmed, I.; Vigovskaya, A.; Fruk, L. Bioconjugate Chem. 2013, 24, 1094
  [ ACS Full Text ], [ CAS], Google Scholar
  44
  Clickable Tyrosine Binding Bifunctional Linkers for Preparation of DNA-Protein Conjugates
  Bauer, Dennis M.; Ahmed, Ishtiaq; Vigovskaya, Antonina; Fruk, Ljiljana
  Bioconjugate Chemistry (2013), 24 (6), 1094-1101CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
  The authors prepd. bifunctional linkers contg. clickable functional groups that enable prepn. of protein-DNA conjugates through binding onto tyrosine residues. Mild conjugation strategy was demonstrated using two proteins, streptavidin (STV) and myoglobin (Mb) and it resulted in conjugates with preserved functionality of both the proteins and DNA strands. Furthermore, protein-DNA conjugates can be successfully immobilized onto solid surface contg. complementary DNA strands and the enzymic activity of Mb-DNA conjugates is even higher than that of corresponding conjugates prepd. through Lys binding.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXot1Glur0%253D&md5=ea7c9c67e6330be49e61e71fc29fd550
45. 45
  Chalker, J. M.; Bernardes, G. J. L.; Davis, B. G. Acc. Chem. Res. 2011, 44, 730
  [ ACS Full Text ], [ CAS], Google Scholar
  45
  A "Tag-and-Modify" Approach to Site-Selective Protein Modification
  Chalker, Justin M.; Bernardes, Goncalo J. L.; Davis, Benjamin G.
  Accounts of Chemical Research (2011), 44 (9), 730-741CODEN: ACHRE4; ISSN:0001-4842. (American Chemical Society)
  A review. Covalent modification can expand a protein's functional capacity. Fluorescent or radioactive labeling, for instance, allows imaging of a protein in real time. Labeling with an affinity probe enables isolation of target proteins and other interacting mols. At the other end of this functional spectrum, protein structures can be naturally altered by enzymic action. Protein-protein interactions, genetic regulation, and a range of cellular processes are under the purview of these post-translational modifications. The ability of protein chemists to install these covalent addns. selectively has been crit. for elucidating their roles in biol. Frequently the transformations must be applied in a site-specific manner, which demands the most selective chem. In this Account, we discuss the development and application of such chem. in our lab. A centerpiece of our strategy is a "tag-and-modify" approach, which entails sequential installation of a uniquely reactive chem. group into the protein (the "tag") and the selective or specific modification of this group. The chem. tag can be a natural or unnatural amino acid residue. Of the natural residues, cysteine is the most widely used as a tag. Early work in our program focused on selective disulfide formation in the synthesis of glycoproteins. For certain applications, the susceptibility of disulfides to redn. was a limitation and prompted the development of several methods for the synthesis of more stable thioether modifications. The desulfurization of disulfides and conjugate addn. to dehydroalanine are two routes to these modifications. The dehydroalanine tag has since proven useful as a general precursor to many modifications after conjugate addn. of various nucleophiles; phosphorylated, glycosylated, peptidylated, prenylated, and even mimics of methylated and acetylated lysine-contg. proteins are all accessible from dehydroalanine. While cysteine is a useful tag for selective modification, unnatural residues present the opportunity for bio-orthogonal chem. Azide-, arylhalide-, alkyne-, and alkene-contg. amino acids can be incorporated into proteins genetically and can be specifically modified through various transformations. These transformations often rely on metal catalysis. The Cu-catalyzed azide-alkyne addn., Ru-catalyzed olefin metathesis, and Pd-catalyzed cross-coupling are examples of such transformations. In the course of adapting these reactions to protein modification, we learned much about the behavior of these reactions in water, and in some cases entirely new catalysts were developed. Through a combination of these bio-orthogonal transformations from the panel of tag-and-modify reactions, multiple and distinct modifications can be installed on protein surfaces. Multiple modifications are common in natural systems, and synthetic access to these proteins has enabled study of their biol. role. Throughout these investigations, much has been learned in chem. and biol. The demands of selective protein modification have revealed many aspects of reaction mechanisms, which in turn have guided the design of reagents and catalysts that allow their successful deployment in water and in biol. milieu. With this ability to modify proteins, it is now possible to interrogate biol. systems with precision that was not previously possible.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXlvFCmtb8%253D&md5=6dc1df95902cb75e3f190f6721e621e1
46. 46
  Boutureira, O.; Bernardes, G. J. L.; Fernández-González, M.; Anthony, D. C.; Davis, B. G. Angew. Chem., Int. Ed. 2012, 51, 1432
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  46
  Selenenylsulfide-linked Homogeneous Glycopeptides and Glycoproteins: Synthesis of Human "Hepatic Se Metabolite A"
  Boutureira, Omar; Bernardes, Goncalo J. L.; Fernandez-Gonzalez, Marta; Anthony, Daniel C.; Davis, Benjamin G.
  Angewandte Chemie, International Edition (2012), 51 (6), 1432-1436, S1432/1-S1432/46CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
  The authors present the synthesis of selenenylsulfide-linked (glycosyl-SeS-Cys) glycopeptides and glycoproteins using a Cys-specific selenylation protocol of cysteine moiety in peptides and proteins, resp. The first synthesis and full characterization of human hepatic Se metabolite A, 5, is also reported.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XitVegsw%253D%253D&md5=2d183abedd5298ab09420005485ecf1c
47. 47
  (a) Chalker, J. M.; Gunnoo, S. B.; Boutureira, O.; Gerstberger, S. C.; Fernández-González, M.; Bernardes, G. J. L.; Griffin, L.; Hailu, H.; Schofield, C. J.; Davis, B. G. Chem. Sci. 2011, 2, 1666
  [ Crossref], [ CAS], Google Scholar
  47a
  Methods for converting cysteine to dehydroalanine on peptides and proteins
  Chalker, Justin M.; Gunnoo, Smita B.; Boutureira, Omar; Gerstberger, Stefanie C.; Fernandez-Gonzalez, Marta; Bernardes, Goncalo J. L.; Griffin, Laura; Hailu, Hanna; Schofield, Christopher J.; Davis, Benjamin G.
  Chemical Science (2011), 2 (9), 1666-1676CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)
  Dehydroalanine is a synthetic precursor to a wide array of protein modifications. We describe multiple methods for the chem. conversion of cysteine to dehydroalanine on peptides and proteins. The scope and limitations of these methods were investigated with attention paid to side reactions, scale, and aq.- and bio-compatibility. The most general method investigated-a bis-alkylation-elimination of cysteine to dehydroalanine-was applied successfully to multiple proteins and enabled the site-selective synthesis of a glycosylated antibody.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXpvFCms74%253D&md5=58e4b225561dc8cc2a6248bb31cd4758
  (b) Bernardes, G. J. L.; Chalker, J. M.; Errey, J. C.; Davis, B. G. J. Am. Chem. Soc. 2008, 130, 5052
  [ ACS Full Text ], [ CAS], Google Scholar
  47b
  Facile Conversion of Cysteine and Alkyl Cysteines to Dehydroalanine on Protein Surfaces: Versatile and Switchable Access to Functionalized Proteins
  Bernardes, Goncalo J. L.; Chalker, Justin M.; Errey, James C.; Davis, Benjamin G.
  Journal of the American Chemical Society (2008), 130 (15), 5052-5053CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  An efficient and robust oxidative elimination of cysteine to dehydroalanine has been discovered. The reaction is induced by O-mesitylenesulfonylhydroxylamine (MSH) and is compatible with methionine. The key elimination has been executed on protein surfaces and allows ready access to different post-translationally modified proteins through conjugate addn. of sulfur nucleophiles to dehydroalanine. Treatment of the resulting thioether with MSH results in regeneration of dehydroalanine, allowing a "functional switch" by subsequent addn. of a different thiol.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXjslahur8%253D&md5=94379dc2edaed8511e00098c6f89fac9
  (c) Bernardes, G. J. L.; Grayson, E. J.; Thompson, S.; Chalker, J. M.; Errey, J. C.; Oualid, F. E.; Claridge, T. D. W.; Davis, B. G. Angew. Chem., Int. Ed. 2008, 47, 2244
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  47c
  From disulfide- to thioether-linked glycoproteins
  Bernardes, Goncalo J. L.; Grayson, Elizabeth J.; Thompson, Sam; Chalker, Justin M.; Errey, James C.; ElOualid, Farid; Claridge, Timothy D. W.; Davis, Benjamin G.
  Angewandte Chemie, International Edition (2008), 47 (12), 2244-2247CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
  The introduction of a thiol tag in combination with chemoselective ligation to form a disulfide-linked bioconjugate is a selective and useful method for site-selective protein glycosylation. The phosphine-mediated desulfurization of such glycoconjugates to their reductant-resistant thioether-linked counterparts completes a convergent, site-selective synthesis of thioether-linked glycoproteins.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXktV2rt74%253D&md5=ba3211b263edd152d3e5ac348ec84c06
48. 48
  Haj-Yahya, N.; Hemantha, H. P.; Meledin, R.; Bondalapati, S.; Seenaiah, M.; Brik, A. Org. Lett. 2014, 16, 540
  [ ACS Full Text ], [ CAS], Google Scholar
  48
  Dehydroalanine-Based Diubiquitin Activity Probes
  Haj-Yahya, Najat; Hemantha, Hosahalli P.; Meledin, Roman; Bondalapati, Somasekhar; Seenaiah, Mallikanti; Brik, Ashraf
  Organic Letters (2014), 16 (2), 540-543CODEN: ORLEF7; ISSN:1523-7052. (American Chemical Society)
  A strategy for the synthesis of dehydroalanine based diubiquitin activity probes is described. The site-specific introduction of dehydroalanine was achieved from diubiquitin bearing Cys residue near the scissile bond between two ubiquitins linked through Lys48, Lys63 or in a head to tail fashion. The probes were characterized for their activities with various deubiquitinases, which open new opportunities in studying deubiquitinases in various settings.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhvFymsb7M&md5=62fad59df71f0444388efbe310aaca72
49. 49
  Boutureira, O.; Bernardes, G. J. L.; D’Hooge, F.; Davis, B. G. Chem. Commun. 2011, 47, 10010
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  49
  Direct radiolabelling of proteins at cysteine using [18F]-fluorosugars
  Boutureira, Omar; Bernardes, Goncalo J. L.; D'Hooge, Francois; Davis, Benjamin G.
  Chemical Communications (Cambridge, United Kingdom) (2011), 47 (36), 10010-10012CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
  A strategy for the site-specific attachment of 2-deoxy-2-fluorosugars to cysteine and dehydroalanine tagged proteins is reported. When combined with thionation of fluorosugars, such as the widely available 18F probe 2-deoxy-2-[18F]fluoroglucose ([18F]FDG), this methodol. allows fast and direct access to site-specific [18F]FDG-labeled proteins.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhtV2htrrK&md5=1e4e04570c0d0df64792885d1e85b5d5
50. 50
  Kunstelj, M.; Fidler, K.; Škrajnar, Š.; Kenig, M.; Smilović, V.; Kusterle, M.; Caserman, S.; Zore, I.; Porekar, V. G.; Jevševar, S. Bioconjugate Chem. 2013, 24, 889
  [ ACS Full Text ], [ CAS], Google Scholar
  50
  Cysteine-Specific PEGylation of rhG-CSF via Selenylsulfide Bond
  Kunstelj, Menci; Fidler, Katarina; Skrajnar, Spela; Kenig, Maja; Smilovic, Vanja; Kusterle, Mateja; Caserman, Simon; Zore, Irena; Porekar, Vladka Gaberc; Jevsevar, Simona
  Bioconjugate Chemistry (2013), 24 (6), 889-896CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
  A new PEGylation reagent enabling selective modification of free thiol groups is described in this article. The reagent was synthesized by attaching linear polyethylene glycol (PEG) N-hydroxysuccinimide to selenocystamine. The reaction was very fast, resulting in over 95% conversion yield. The active group of this new PEG-Se reagent is a diselenide, reacting with thiols via thiol/diselenide exchange reaction. Recombinant human granulocyte colony-stimulating factor (rhG-CSF) with an unpaired cysteine at the position 18 (Cys18) was used as a model protein. It was comparatively PEGylated with the new PEG-Se reagent, as well as with com. available maleimide (PEG-Mal) and ortho-pyridyl disulfide (PEG-OPSS) PEG reagents. The highest PEGylation yield was obtained with PEG-Mal, followed by PEG-OPSS and PEG-Se. The reaction rates of PEG-Mal and PEG-Se were comparable, while the reaction rate of PEG-OPSS was lower. Purified monoPEGylated rhG-CSF conjugates were characterized and compared. Differences in activity, stability, and in vivo performance were obsd., although all conjugates contained a 20 kDa PEG attached to the Cys18. Minor conformational changes were obsd. in the conjugate prepd. with PEG-Mal. These changes were also reflected in low in vitro biol. activity and aggregate formation of the maleimide conjugate. The conjugate prepd. with PEG-Se had the highest in vitro biol. activity, while the conjugate prepd. with PEG-OPSS had the best in vivo performance.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXmt1ylt70%253D&md5=e753b238a06104579e8819367cd65919
51. 51
  Grayson, E. J.; Bernardes, G. J. L.; Chalker, J. M.; Boutureira, O.; Koeppe, J. R.; Davis, B. G. Angew. Chem., Int. Ed. 2011, 50, 4127
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  51
  A Coordinated Synthesis and Conjugation Strategy for the Preparation of Homogeneous Glycoconjugate Vaccine Candidates
  Grayson, Elizabeth J.; Bernardes, Goncalo J. L.; Chalker, Justin M.; Boutureira, Omar; Koeppe, Julia R.; Davis, Benjamin G.
  Angewandte Chemie, International Edition (2011), 50 (18), 4127-4132, S4127/1-S4127/92CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
  A strategy for the prepn. of glycoconjugated vaccines in which the site of attachment is well defined permitting site-specific protein conjugation is presented. Glycosyl disulfides are beneficial glycosyl donors for the synthesis of precursor oligosaccharides. Their aglycon flexibility allows a straightforward iterative assembly of complex carbohydrates contg. protective group freedom. Furthermore, the glycosyl disulfides advantageously deliver the thiol products suitable for site-specific protein ligation. Finally, since the use of pure, well-defined glycoproteins as potential immunogens is rare, this ability will allow insight into the effect of epitope positioning and immune response.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXkvFyrtLc%253D&md5=335c7b81ca4654ffc6d82ee8c1b1f574
52. 52
  Chalker, J. M.; Lercher, L.; Rose, N. R.; Schofield, C. J.; Davis, B. G. Angew. Chem., Int. Ed. 2012, 51, 1835
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  52
  Conversion of Cysteine into Dehydroalanine Enables Access to Synthetic Histones Bearing Diverse Post-Translational Modifications
  Chalker, Justin M.; Lercher, Lukas; Rose, Nathan R.; Schofield, Christopher J.; Davis, Benjamin G.
  Angewandte Chemie, International Edition (2012), 51 (8), 1835-1839, S1835/1-S1835/73CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
  We have shown that Dha (dehydroalanine) is readily installed in histones by the reaction of the dibromide reagent 1 (a,a'-di-bromo-adipyl(bis)amide) with genetically incorporated Cys residues. Dha, in turn, is a chem. precursor to mimics of six distinct PTMs (post-translational modifications): mono-, di-, and trimethylated lysine, acetylated lysine, phosphorylated serine, and glycosylated serine. Through their combined use, we have shown ready switching of site and PTM type. The same modification could also be installed at multiple sites on a multi-milligram scale. To illustrate the potential of this technol., the first validation of phosphocysteine as a mimic of phosphoserine in any protein was described, the first access to a glycosylated histone was enabled, and the first direct observation of HDAC activity on an acetylated lysine mimic was reported for a full-length histone. The demonstrated interaction of our synthetic modified histones with both readers and writer/erasers shown here is a key step. Currently, we are exploring the use of the modified histones reported here as substrates for other chromatin-modifying enzymes.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xnt1ymsA%253D%253D&md5=db2acb39ab1d8da2380b137e70937a60
53. 53
  Fernández-González, M.; Boutureira, O.; Bernardes, G. J. L.; Chalker, J. M.; Young, M. A.; Errey, J. C.; Davis, B. G. Chem. Sci. 2010, 709
  [ Crossref], [ CAS], Google Scholar
  53
  Site-selective chemoenzymatic construction of synthetic glycoproteins using endoglycosidases
  Fernandez-Gonzalez, Marta; Boutureira, Omar; Bernardes, Goncalo J. L.; Chalker, Justin M.; Young, Matthew A.; Errey, James C.; Davis, Benjamin G.
  Chemical Science (2010), 1 (6), 709-715CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)
  Combined chem. tagging followed by Endo-A catalyzed elongation allows access to homogeneous, elaborated glycoproteins. A survey of different linkages and sugars demonstrated not only that unnatural linkages can be tolerated but they can provide insight into the scope of Endo-A transglycosylation activity. S-linked GlcNAc-glycoproteins are useful substrates for Endo-A extensions and display enhanced stability to hydrolysis at exposed sites. O-CH2-triazole-linked GlcNAc-glycoproteins derived from azidohomoalanine-tagged protein precursors were found to be optimal at sterically demanding sites.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhtl2nsLnE&md5=613c61342fa65cd1273e79866d7bead4
54. 54
  Aydillo, C.; Compañón, I.; Avenoza, A.; Busto, J. H.; Corzana, F.; Peregrina, J. M.; Zurbano, M. M. J. Am. Chem. Soc. 2014, 136, 789
  [ ACS Full Text ], [ CAS], Google Scholar
  54
  S-Michael Additions to Chiral Dehydroalanines as an Entry to Glycosylated Cysteines and a Sulfa-Tn Antigen Mimic
  Aydillo, Carlos; Companon, Ismael; Avenoza, Alberto; Busto, Jesus H.; Corzana, Francisco; Peregrina, Jesus M.; Zurbano, Maria M.
  Journal of the American Chemical Society (2014), 136 (2), 789-800CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  Stereoselective sulfa-Michael addn. of appropriately protected thiocarbohydrates to chiral dehydroalanines has been developed as a key step in the synthesis of biol. important cysteine derivs., such as S-(β-D-glucopyranosyl)-D-cysteine, which has not been synthesized to date, and S-(2-acetamido-2-deoxy-α-D-galactopyranosyl)-L-cysteine, which could be considered as a mimic of Tn antigen. The corresponding diamide deriv. was also synthesized and analyzed from a conformational viewpoint, and its bound state with a lectin was studied.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXksVGm&md5=24177394496816c3440202ebe43941ce
55. 55
  Junutula, J. R.; Raab, H.; Clark, S.; Bhakta, S.; Leipold, D. D.; Weir, S.; Chen, Y.; Simpson, M.; Tsai, S. P.; Dennis, M. S.; Lu, Y.; Meng, Y. G.; Ng, C.; Yang, J.; Lee, C. C.; Duenas, E.; Gorrell, J.; Katta, V.; Kim, A.; McDorman, K.; Flagella, K.; Venook, R.; Ross, S.; Spencer, S. D.; Lee Wong, W.; Lowman, H. B.; Vandlen, R.; Sliwkowski, M. X.; Scheller, R. H.; Polakis, P.; Mallet, W. Nat. Biotechnol. 2008, 26, 925
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  55
  Site-specific conjugation of a cytotoxic drug to an antibody improves the therapeutic index
  Junutula, Jagath R.; Raab, Helga; Clark, Suzanna; Bhakta, Sunil; Leipold, Douglas D.; Weir, Sylvia; Chen, Yvonne; Simpson, Michelle; Tsai, Siao Ping; Dennis, Mark S.; Lu, Yanmei; Meng, Y. Gloria; Ng, Carl; Yang, Jihong; Lee, Chien C.; Duenas, Eileen; Gorrell, Jeffrey; Katta, Viswanatham; Kim, Amy; McDorman, Kevin; Flagella, Kelly; Venook, Rayna; Ross, Sarajane; Spencer, Susan D.; Wong, Wai Lee; Lowman, Henry B.; Vandlen, Richard; Sliwkowski, Mark X.; Scheller, Richard H.; Polakis, Paul; Mallet, William
  Nature Biotechnology (2008), 26 (8), 925-932CODEN: NABIF9; ISSN:1087-0156. (Nature Publishing Group)
  Antibody-drug conjugates enhance the antitumor effects of antibodies and reduce adverse systemic effects of potent cytotoxic drugs. However, conventional drug conjugation strategies yield heterogeneous conjugates with relatively narrow therapeutic index (max. tolerated dose/curative dose). Using leads from the authors' previously described phage display-based method to predict suitable conjugation sites, the authors engineered cysteine substitutions at positions on light and heavy chains that provide reactive thiol groups and do not perturb Ig folding and assembly, or alter antigen binding. When conjugated to monomethyl auristatin E, an antibody against the ovarian cancer antigen MUC16 is as efficacious as a conventional conjugate in mouse xenograft models. Moreover, it is tolerated at higher doses in rats and cynomolgus monkeys than the same conjugate prepd. by conventional approaches. The favorable in vivo properties of the near-homogeneous compn. of this conjugate suggest that this strategy offers a general approach to retaining the antitumor efficacy of antibody-drug conjugates, while minimizing their systemic toxicity.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXps1Wmu7s%253D&md5=d55f59594fb6349d0337dfed2783e83c
56. 56
  (a) Steiner, M.; Hartmann, I.; Perrino, E.; Casi, G.; Brighton, S.; Jelesarov, I.; Bernardes, G. J. L.; Neri, D. Chem. Sci. 2013, 4, 297
  [ Crossref], [ CAS], Google Scholar
  56a
  Spacer length shapes drug release and therapeutic efficacy of traceless disulfide-linked ADCs targeting the tumor neovasculature
  Steiner, Martina; Hartmann, Isabelle; Perrino, Elena; Casi, Giulio; Brighton, Samatanga; Jelesarov, Ilian; Bernardes, Goncalo J. L.; Neri, Dario
  Chemical Science (2013), 4 (1), 297-302CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)
  We systematically investigated how the therapeutic efficacy of a traceless, vascular targeting antibody-drug conjugate (ADC) is affected by the length of a spacer introduced between the antibody's globular fold and the site of drug attachment. Homogeneous ADCs were prepd. from the direct conjugation of engineered C-terminal cysteines with a potent thiol contg. drug which was sepd. from the antibody surface by unstructured spacers of increasing length. We found that a smaller spacer length is reflected in enhanced stability and therapeutic efficacy of the conjugates in a syngeneic model of murine cancer.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhslKkurnM&md5=e4263b7e14041d12e46b0098868c40a0
  (b) Bernardes, G. J. L.; Casi, G.; Trüssel, S.; Hartmann, I.; Schwager, K.; Scheuermann, J.; Neri, D. Angew. Chem., Int. Ed. 2012, 51, 941
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  56b
  A Traceless Vascular-Targeting Antibody-Drug Conjugate for Cancer Therapy
  Bernardes, Goncalo J. L.; Casi, Giulio; Truessel, Sabrina; Hartmann, Isabelle; Schwager, Kathrin; Scheuermann, Joerg; Neri, Dario
  Angewandte Chemie, International Edition (2012), 51 (4), 941-944, S941/1-S941/42CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
  Monoclonal antibodies have demonstrated considerable utility in the clin. treatment of cancer, but unmodified Igs are rarely curative, esp. when used as single agents. Thus, there is considerable interest in arming antibodies with bioactive payloads (e.g., drugs, radionuclides, cytokines), to improve their potency and selectivity, thus increasing activity at the tumor site while sparing normal tissues. However, monoclonal antibodies specific to tumor cell antigens often exhibit limited diffusion into the solid tumor mass by several mechanisms, including slow extravasation and antibody trapping by perivascular tumor cells (the so-called antigen barrier). In view of the fact that the formation of new blood vessels (angiogenesis) is a rare process in a healthy adult but a characteristic feature of virtually all types of aggressive cancers, it would be reasonable to develop vascular-targeting antibody-dug conjugates (ADCs). In conclusion, a novel approach for the delivery of cytotoxic drugs using ADCs has been developed. Current ADCs target tumor cell surface markers and rely on the DC being internalized in the cells for drug delivery. Instead, our approach relies on targeting the tumor neo-vasculature offering comprehensive tumoral coverage.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhs1elurvI&md5=ca90b850dfb9fe9ce8ca598d694cf79b
  (c) Perrino, E.; Steiner, M.; Krall, N.; Bernardes, G. J. L.; Pretto, F.; Casi, G.; Neri, D. Cancer Res. 2014, 74, 2569
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  56c
  Curative Properties of Noninternalizing Antibody-Drug Conjugates Based on Maytansinoids
  Perrino, Elena; Steiner, Martina; Krall, Nikolaus; Bernardes, Goncalo J. L.; Pretto, Francesca; Casi, Giulio; Neri, Dario
  Cancer Research (2014), 74 (9), 2569-2578CODEN: CNREA8; ISSN:0008-5472. (American Association for Cancer Research)
  It is generally thought that the anticancer efficacy of antibody-drug conjugates (ADC) relies on their internalization by cancer cells. However, recent work on an ADC that targets fibronectin in the tumor microenvironment suggests this may not be necessary. The alternatively spliced extra domains A and B (EDA and EDB) of fibronectin offer appealing targets for ADC development, because the antigen is strongly expressed in many solid human tumors and nearly undetectable in normal tissues except for the female reproductive system. In this study, we describe the properties of a set of ADCs based on an antibody targeting the alternatively spliced EDA of fibronectin coupled to one of a set of potent cytotoxic drugs (DM1 or one of two duocarmycin derivs.). The DM1 conjugate SIP(F8)-SS-DM1 mediated potent antitumor activity in mice bearing DMl-sensitive F9 tumors but not DMl-insensitive CT26 tumors. Quant. biodistribution studies and microscopic analyses confirmed a preferential accumulation of SIP(F8)-SS-DM1 in the subendothelial extracellular matrix of tumors, similar to the pattern obsd. for unmodified antibody. Notably, we found that treatments were well tolerated at efficacious doses that were fully curative and compatible with pharmaceutical development. Our findings offer a preclin. proof-of-concept for curative ADC targeting the tumor microenvironment that do not rely upon antigen internalization.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXnt1arsro%253D&md5=183cf5ce0d4c3b74ebb0538f0233c0f6
  (d) Bernardes, G. J. L.; Steiner, M.; Hartmann, I.; Neri, D.; Casi, G. Nat. Protoc. 2013, 8, 2079
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  56d
  Site-specific chemical modification of antibody fragments using traceless cleavable linkers
  Bernardes, Goncalo J. L.; Steiner, Martina; Hartmann, Isabelle; Neri, Dario; Casi, Giulio
  Nature Protocols (2013), 8 (11), 2079-2089CODEN: NPARDW; ISSN:1750-2799. (Nature Publishing Group)
  Antibody-drug conjugates (ADCs) are promising agents for the selective delivery of cytotoxic drugs to specific cells (for example, tumors). In this protocol, we describe two strategies for the precise modification at engineered C- or N-terminal cysteines of antibodies in IgG, diabody and small immunoprotein (SIP) formats that yield homogenous ADCs. In this protocol, cemadotin derivs. are used as model drugs, as these agents have a potent cytotoxic activity and are easy to synthesize. However, other drugs with similar functional groups could be considered. In the first approach, a cemadotin deriv. contg. a sulfhydryl group results in a mixed disulfide linkage. In the second approach, a cemadotin deriv. contg. an aldehyde group is joined via a thiazolidine linkage. The procedures outlined are robust, enabling the prepn. of ADCs with a defined no. of drugs per antibody in a time frame between 7 and 24 h.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhsFGqtrfJ&md5=b878287531b0d108a73b802f3302dbfa
57. 57
  Casi, G.; Huguenin-Dezot, N.; Zuberbühler, K.; Scheuermann, J. r.; Neri, D. J. Am. Chem. Soc. 2012, 134, 5887
  [ ACS Full Text ], [ CAS], Google Scholar
  57
  Site-Specific Traceless Coupling of Potent Cytotoxic Drugs to Recombinant Antibodies for Pharmacodelivery
  Casi, Giulio; Huguenin-Dezot, Nicolas; Zuberbuhler, Kathrin; Scheuermann, Jorg; Neri, Dario
  Journal of the American Chemical Society (2012), 134 (13), 5887-5892CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  Aldehyde drugs are gaining increasing research interest, considering that aldehyde dehydrogenases overexpression is characteristic of cancer stem cells. Here, we describe the traceless site-specific coupling of a novel potent drug, contg. an aldehyde moiety, to recombinant antibodies, which were engineered to display a cysteine residue at their N-terminus, or a 1,2-aminothiol at their C-terminus. The resulting chem. defined antibody-drug conjugates represent the first example in which a thiazolidine linkage is used for the targeted delivery and release of cytotoxic agents.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xjt1OgtLY%253D&md5=bb33caba8b47db0a47d3143d63655aa5
58. 58
  Yuan, Y.; Liang, G. Org. Biomol. Chem. 2014, 12, 865
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  58
  A biocompatible, highly efficient click reaction and its applications
  Yuan, Yue; Liang, Gaolin
  Organic & Biomolecular Chemistry (2014), 12 (6), 865-871CODEN: OBCRAK; ISSN:1477-0520. (Royal Society of Chemistry)
  A review. Herein, we review the development, optimization, applications and potential prospects of a novel click reaction based on the condensation reaction between 2-cyanobenzothiazole (CBT) and D-cysteine (D-Cys) in fireflies. This click condensation reaction has obvious advantages in biocompatibility, efficiency and stability in aq. environments. Optimization of this click reaction has been carried out so that it can be controlled by pH change, redn., or enzymic cleavage to synthesize large mols. and self-assembled nanostructures, or enhance probe signals. Consequently, this CBT-based click reaction has been and could be successfully applied to a wide range of biomedical applications such as mol. imaging (e.g., optical imaging, nuclear imaging and magnetic resonance imaging), biomol. detection, drug delivery and other potentialities.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXnsFWgsQ%253D%253D&md5=9f35b5447ec48f6257b638902dc5875c
59. 59
  (a) Nathani, R. I.; Chudasama, V.; Ryan, C. P.; Moody, P. R.; Morgan, R. E.; Fitzmaurice, R. J.; Smith, M. E. B.; Baker, J. R.; Caddick, S. Org. Biomol. Chem. 2013, 11, 2408
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  59a
  Reversible protein affinity-labelling using bromomaleimide-based reagents
  Nathani, Ramiz I.; Chudasama, Vijay; Ryan, Chris P.; Moody, Paul R.; Morgan, Rachel E.; Fitzmaurice, Richard J.; Smith, Mark E. B.; Baker, James R.; Caddick, Stephen
  Organic & Biomolecular Chemistry (2013), 11 (15), 2408-2411CODEN: OBCRAK; ISSN:1477-0520. (Royal Society of Chemistry)
  Reversible protein biotinylation is readily affected via conjugation with a bromomaleimide-based reagent followed by reductive cleavage. The intermediate biotinylated protein constructs are stable at physiol. temp. and pH 8.0. Quant. reversibility is elegantly delivered under mild conditions of using a stoichiometric amt. of a bis-thiol, thus providing an approach that will be of general interest in chem. biol. and proteomics.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXktlKisbY%253D&md5=a87a9d55027d35f95b095697601fb299
  (b) Smith, M. E. B.; Schumacher, F. F.; Ryan, C. P.; Tedaldi, L. M.; Papaioannou, D.; Waksman, G.; Caddick, S.; Baker, J. R. J. Am. Chem. Soc. 2010, 132, 1960
  [ ACS Full Text ], [ CAS], Google Scholar
  59b
  Protein Modification, Bioconjugation, and Disulfide Bridging Using Bromomaleimides
  Smith, Mark E. B.; Schumacher, Felix F.; Ryan, Chris P.; Tedaldi, Lauren M.; Papaioannou, Danai; Waksman, Gabriel; Caddick, Stephen; Baker, James R.
  Journal of the American Chemical Society (2010), 132 (6), 1960-1965CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  The maleimide motif is widely used for the selective chem. modification of cysteine residues in proteins. Despite widespread utilization, there are some potential limitations, including the irreversible nature of the reaction and, hence, the modification and the no. of attachment positions. The authors conceived of a new class of maleimide which would address some of these limitations and provide new opportunities for protein modification. The authors report herein the use of mono- and dibromomaleimides for reversible cysteine modification and illustrate this on the SH2 domain of the Grb2 adaptor protein (L111C). After initial modification of a protein with a bromo- or dibromomaleimide, it is possible to add an equiv. of a second thiol to give further bioconjugation, demonstrating that bromomaleimides offer opportunities for up to three points of attachment. The resultant protein-maleimide products can be cleaved to regenerate the unmodified protein by addn. of a phosphine or a large excess of a thiol. Furthermore, dibromomaleimide can insert into a disulfide bond, forming a maleimide bridge, and this is illustrated on the peptide hormone somatostatin. Fluorescein-labeled dibromomaleimide is synthesized and inserted into the disulfide to construct a fluorescent somatostatin analog. These results highlight the significant potential for this new class of reagents in protein modification.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXptl2rug%253D%253D&md5=0ed793a9db6ef7384d8b64294d0cecc8
60. 60
  Moody, P.; Smith, M. E. B.; Ryan, C. P.; Chudasama, V.; Baker, J. R.; Molloy, J.; Caddick, S. ChemBioChem 2012, 13, 39
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  60
  Bromomaleimide-Linked Bioconjugates Are Cleavable in Mammalian Cells
  Moody, Paul; Smith, Mark. E. B.; Ryan, Chris P.; Chudasama, Vijay; Baker, James R.; Molloy, Justin; Caddick, Stephen
  ChemBioChem (2012), 13 (1), 39-41CODEN: CBCHFX; ISSN:1439-4227. (Wiley-VCH Verlag GmbH & Co. KGaA)
  The synthesis of bromomaleimide-linked bioconjugates was carried out to demonstrate that bromomaleimide-linked bioconjugates were cleaved in the cytoplasm of mammalian cells.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhsVOktL7N&md5=be902af98c65c468943336de07dfdf94
61. 61
  Marculescu, C.; Kossen, H.; Morgan, R. E.; Mayer, P.; Fletcher, S. A.; Tolner, B.; Chester, K. A.; Jones, L. H.; Baker, J. R. Chem. Commun. 2014, 50, 7139
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  61
  Aryloxymaleimides for cysteine modification, disulfide bridging and the dual functionalization of disulfide bonds
  Marculescu, Cristina; Kossen, Hanno; Morgan, Rachel E.; Mayer, Patrick; Fletcher, Sally A.; Tolner, Berend; Chester, Kerry A.; Jones, Lyn H.; Baker, James R.
  Chemical Communications (Cambridge, United Kingdom) (2014), 50 (54), 7139-7142CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
  Tuning the properties of maleimide reagents holds significant promise in expanding the toolbox of available methods for bioconjugation. Herein the authors describe aryloxymaleimides which represent next generation maleimides of attenuated reactivity and demonstrate their ability to enable new methods for protein modification at disulfide bonds.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtVagt7fK&md5=b1149186edd6b0e678b4beb8e7d4f72a
62. 62
  (a) Lyon, R. P.; Setter, J. R.; Bovee, T. D.; Doronina, S. O.; Hunter, J. H.; Anderson, M. E.; Balasubramanian, C. L.; Duniho, S. M.; Leiske, C. I.; Li, F.; Senter, P. D. Nat. Biotechnol. 2014, 32, 1059
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  62a
  Self-hydrolyzing maleimides improve the stability and pharmacological properties of antibody-drug conjugates
  Lyon, Robert P.; Setter, Jocelyn R.; Bovee, Tim D.; Doronina, Svetlana O.; Hunter, Joshua H.; Anderson, Martha E.; Balasubramanian, Cindy L.; Duniho, Steven M.; Leiske, Chris I.; Li, Fu; Senter, Peter D.
  Nature Biotechnology (2014), 32 (10), 1059-1062CODEN: NABIF9; ISSN:1087-0156. (Nature Publishing Group)
  Many antibody-drug conjugates (ADCs) are unstable in vivo because they are formed from maleimide-contg. components conjugated to reactive thiols. These thiosuccinimide linkages undergo two competing reactions in plasma: elimination of the maleimide through a retro-Michael reaction, which results in loss of drug-linker from the ADC, and hydrolysis of the thiosuccinimide ring, which results in a deriv. that is resistant to the elimination reaction. In an effort to create linker technologies with improved stability characteristics, we used diaminopropionic acid (DPR) to prep. a drug-linker incorporating a basic amino group adjacent to the maleimide, positioned to provide intramol. catalysis of thiosuccinimide ring hydrolysis. This basic group induces the thiosuccinimide to undergo rapid hydrolysis at neutral pH and room temp. Once hydrolyzed, the drug-linker is no longer subject to maleimide elimination reactions, preventing nonspecific deconjugation. In vivo studies demonstrate that the increased stability characteristics can lead to improved ADC antitumor activity and reduced neutropenia.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsFKms7jN&md5=96c3b19b856cc9c685cbdc704a842797
  (b) Tumey, L. N.; Charati, M.; He, T.; Sousa, E.; Ma, D.; Han, X.; Clark, T.; Casavant, J.; Loganzo, F.; Barletta, F.; Lucas, J.; Graziani, E. I. Bioconjugate Chem. 2014, 25, 1871
  [ ACS Full Text ], [ CAS], Google Scholar
  62b
  Mild Method for Succinimide Hydrolysis on ADCs: Impact on ADC Potency, Stability, Exposure, and Efficacy
  Tumey, L. Nathan; Charati, Manoj; He, Tao; Sousa, Eric; Ma, Dangshe; Han, Xiaogang; Clark, Tracey; Casavant, Jeff; Loganzo, Frank; Barletta, Frank; Lucas, Judy; Graziani, Edmund I.
  Bioconjugate Chemistry (2014), 25 (10), 1871-1880CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
  The stability of the connection between the antibody and the toxin can have a profound impact on ADC safety and efficacy. There has been increasing evidence in recent years that maleimide-based ADCs are prone to payload loss via a retro-Michael type reaction. Herein, we report a mild method for the hydrolysis of the succinimide-thioether ring which results in a "ring-opened" linker. ADCs contg. this hydrolyzed succinimide linker show equiv. cytotoxicity, improved in vitro stability, improved PK exposure, and improved efficacy as compared to their nonhydrolyzed counterparts. This method offers a simple way to improve the stability, exposure, and efficacy of maleimide-based ADCs.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsFelsb3F&md5=a680174dc91b2ce9a3c72b6519a6c231
  (c) Fontaine, S. D.; Reid, R.; Robinson, L.; Ashley, G. W.; Santi, D. V. Bioconjugate Chem. 2015, 26, 145
  [ ACS Full Text ], [ CAS], Google Scholar
  62c
  Long-Term Stabilization of Maleimide-Thiol Conjugates
  Fontaine, Shaun D.; Reid, Ralph; Robinson, Louise; Ashley, Gary W.; Santi, Daniel V.
  Bioconjugate Chemistry (2015), 26 (1), 145-152CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
  The rates of ring-opening hydrolysis and retro-Michael/Michael addn. (thiol exchange) of N-substituted succinimide thioethers formed by maleimide-thiol conjugation with glutathione and the effects of their maleimide nitrogen substituents on the rates of maleimide hydrolysis and retro-Michael/Michael addn. reactions were detd. Ring-opening of conjugates prepd. with commonly used maleimides were too slow to serve as prevention against thiol exchange; however, the ring-opening rates of maleimides were greatly accelerated by electron withdrawing N-substituents, and the products had half-lives of over two years. The PEGylated antibody Cimzia underwent ring-opening and retro-Michael addns. with rates consistent with model compds. except for the difference in acidity of the internal cysteine thiol of Cimizia's antibody vs. the nearly terminal cysteine thiols of the model compds. Thus, conjugates (particularly antibody-drug conjugates prepd. as drugs) made with maleimides possessing electron-deficient nitrogen substituents can be purposefully hydrolyzed to their ring-opened counterparts in vitro to ensure their in vivo stability to thiol cleavage and exchange reactions.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXitFCrsrfN&md5=ab4fcacf5f9f58159bafa50353eab4d5
63. 63
  Chudasama, V.; Smith, M. E. B.; Schumacher, F. F.; Papaioannou, D.; Waksman, G.; Baker, J. R.; Caddick, S. Chem. Commun. 2011, 47, 8781
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  63
  Bromopyridazinedione-mediated protein and peptide bioconjugation
  Chudasama, Vijay; Smith, Mark E. B.; Schumacher, Felix F.; Papaioannou, Danai; Waksman, Gabriel; Baker, James R.; Caddick, Stephen
  Chemical Communications (Cambridge, United Kingdom) (2011), 47 (31), 8781-8783CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
  Bromopyridazinedione-mediated bioconjugation to a cysteine contg. protein and a disulfide contg. peptide is described. The conjugates are cleavable in an excess of thiol, including cytoplasmically-relevant concns. of glutathione, and show a high level of hydrolytic stability. The constructs have the potential for four points of chem. attachment.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXpt1Kru7Y%253D&md5=0d8615a135eb11522e0809328902aab4
64. 64
  Maruani, A.; Alom, S.; Canavelli, P.; Lee, M. T. W.; Morgan, R. E.; Chudasama, V.; Caddick, S. Chem. Commun. 2015, DOI: 10.1039/C4CC08515A
  [ Crossref], Google Scholar
  There is no corresponding record for this reference.
65. 65
  Nathani, R.; Moody, P.; Smith, M. E. B.; Fitzmaurice, R. J.; Caddick, S. ChemBioChem 2012, 13, 1283
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  65
  Bioconjugation of Green Fluorescent Protein via an Unexpectedly Stable Cyclic Sulfonium Intermediate
  Nathani, Ramiz; Moody, Paul; Smith, Mark E. B.; Fitzmaurice, Richard J.; Caddick, Stephen
  ChemBioChem (2012), 13 (9), 1283-1285CODEN: CBCHFX; ISSN:1439-4227. (Wiley-VCH Verlag GmbH & Co. KGaA)
  Treatment of a cysteine mutant (S147C) of superfolder green fluorescent protein (GFP) with bis-alkylating agents can be used to prep. highly stable, yet synthetically useful cyclic protein sulfonium adducts. These species undergo clean addn. reactions to allow the introduction of a variety of useful chem. motifs. It was envisaged that the stability of the generated cysteine-derived sulfonium is presumably strongly correlated to the chem. environment of the alkylated cysteine. This new bioconjugation technique could provide a useful entry into multiply functionalized proteins and further work will be directed toward extending these findings to other systems.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XnsFyjur4%253D&md5=e075d1a428cc74bbd50854a882711091
66. 66
  Nathani, R. I.; Moody, P.; Chudasama, V.; Smith, M. E. B.; Fitzmaurice, R. J.; Caddick, S. Chem. Sci. 2013, 4, 3455
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  66
  A novel approach to the site-selective dual labelling of a protein via chemoselective cysteine modification
  Nathani, Ramiz I.; Moody, Paul; Chudasama, Vijay; Smith, Mark E. B.; Fitzmaurice, Richard J.; Caddick, Stephen
  Chemical Science (2013), 4 (9), 3455-3458CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)
  Local protein microenvironment is used to control the outcome of reaction between cysteine residues and 2,5-dibromohexanediamide. The differential reactivity is exploited to introduce two orthogonal reactive handles onto the surface of a double cysteine mutant of superfolder green fluorescent protein in a regioselective manner. Subsequent elaboration with commonly used thiol and alkyne contg. reagents affects site-selective protein dual labeling.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtFOks7jF&md5=5162cef2d39eba5c8944bda9f142cf31
67. 67
  Shiu, H.-Y.; Chan, T.-C.; Ho, C.-M.; Liu, Y.; Wong, M.-K.; Che, C.-M. Chem.—Eur. J. 2009, 15, 3839
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  67
  Electron-deficient alkynes as cleavable reagents for the modification of cysteine-containing peptides in aqueous medium
  Shiu, Hoi-Yan; Chan, Tak-Chung; Ho, Chi-Ming; Liu, Yungen; Wong, Man-Kin; Che, Chi-Ming
  Chemistry - A European Journal (2009), 15 (15), 3839-3850CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)
  An efficient method has been developed for the chemoselective cysteine modification of unprotected peptides and proteins in aq. media through the formation of a vinyl sulfide linkage by using electron-deficient alkynes, including alkynoic amides, esters and alky-nones. The terminal alky-none-modified peptides could be converted back into the unmodified peptides (81% isolated yield) by adding thiols under mild conditions. The usefulness of this thiol-assisted cleavage of the vinyl sulfide linkage in peptides has been exemplified by the enrichment of a cysteine-contg. peptide (71% recovery) from a mixt. of cysteine-contg. and non-cysteine-contg. peptides.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXksleitr0%253D&md5=cdf4acf18e4737c673a807ed1968aae6
68. 68
  Shiu, H.-Y.; Chong, H.-C.; Leung, Y.-C.; Zou, T.; Che, C.-M. Chem. Commun. 2014, 50, 4375
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  68
  Phosphorescent proteins for bio-imaging and site selective bio-conjugation of peptides and proteins with luminescent cyclometalated iridium(iii) complexes
  Shiu, Hoi-Yan; Chong, Hiu-Chi; Leung, Yun-Chung; Zou, Taotao; Che, Chi-Ming
  Chemical Communications (Cambridge, United Kingdom) (2014), 50 (33), 4375-4378CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
  A new bio-conjugation reaction for site selective modification of proteins and peptides with phosphorescent iridium(iii) complexes has been developed; the Ir(iii)-modified proteins and peptides display long emission lifetimes and large Stoke shifts that can be used for bio-imaging studies.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXltFajs7c%253D&md5=ac5e56bacfe9a9c7a40245a97bed6529
69. 69
  Koniev, O.; Leriche, G.; Nothisen, M.; Remy, J.-S.; Strub, J.-M.; Schaeffer-Reiss, C.; Van Dorsselaer, A.; Baati, R.; Wagner, A. Bioconjugate Chem. 2014, 25, 202
  [ ACS Full Text ], [ CAS], Google Scholar
  69
  Selective Irreversible Chemical Tagging of Cysteine with 3-Arylpropiolonitriles
  Koniev, Oleksandr; Leriche, Geoffray; Nothisen, Marc; Remy, Jean-Serge; Strub, Jean-Marc; Schaeffer-Reiss, Christine; Van Dorsselaer, Alain; Baati, Rachid; Wagner, Alain
  Bioconjugate Chemistry (2014), 25 (2), 202-206CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
  Exquisite chemoselectivity for cysteine has been found for a novel class of remarkably hydrolytically stable reagents, 3-arylpropiolonitriles (APN). The efficacy of the APN-mediated tagging was benchmarked against other cysteine-selective methodologies in a model study on a series of traceable amino acid derivs. The selectivity of the methodol. was further explored on peptide mixts. obtained by trypsin digestion of lysozyme. Addnl., the superior stability of APN-cysteine conjugates in aq. media, human plasma, and living cells makes this new thiol-click reaction a promising methodol. for applications in bioconjugation.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXmtl2nsQ%253D%253D&md5=6a55f6f7c3ca774016d6c92c5e21812c
70. 70
  Arumugam, S.; Guo, J.; Mbua, N. E.; Friscourt, F.; Lin, N.; Nekongo, E.; Boons, G.-J.; Popik, V. V. Chem. Sci. 2014, 5, 1591
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  70
  Selective and reversible photochemical derivatization of cysteine residues in peptides and proteins
  Arumugam, Selvanathan; Guo, Jun; Mbua, Ngalle Eric; Friscourt, Frederic; Lin, Nannan; Nekongo, Emmanuel; Boons, Geert-Jan; Popik, Vladimir V.
  Chemical Science (2014), 5 (4), 1591-1598CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)
  The selective derivatization of solvent-exposed cysteine residues in peptides and proteins is achieved by brief irradn. of an aq. soln. contg. 3-(hydroxymethyl)-2-naphthol derivs. (NQMPs) with a 350 nm fluorescent lamp. NQMP can be conjugated with various moieties, such as PEG, dyes, carbohydrates, or possess a fragment for further selective derivatization, e.g., biotin, azide, alkyne, etc. Attractive features of this labeling approach include an exceptionally fast rate of the reaction and a requirement for a low equivalence of the reagent. The NQMP-thioether linkage is stable under ambient conditions, and survives protein digestion and MS anal. Irradn. of an NQMP-labeled protein in a dil. soln. (<40 μM) or in the presence of a vinyl ether results in a traceless release of the substrate. The reversible biotinylation of bovine serum albumin (BSA), as well as the capture and release of this protein using NeutrAvidin Agarose resin beads has been demonstrated.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXjsVekurs%253D&md5=dc009e216182fe84df3741223c380d7d
71. 71
  Zhang, D.; Devarie-Baez, N. O.; Li, Q.; Lancaster, J. R.; Xian, M. Org. Lett. 2012, 14, 3396
  [ ACS Full Text ], [ CAS], Google Scholar
  71
  Methylsulfonyl Benzothiazole (MSBT): A Selective Protein Thiol Blocking Reagent
  Zhang, Dehui; Devarie-Baez, Nelmi O.; Li, Qian; Lancaster, Jack R.; Xian, Ming
  Organic Letters (2012), 14 (13), 3396-3399CODEN: ORLEF7; ISSN:1523-7052. (American Chemical Society)
  A new thiol blocking reagent, methylsulfonyl benzothiazole, was discovered. This reagent showed good selectivity and high reactivity for protein thiols.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xot1antL8%253D&md5=6e785b51e6288197559db5a91a982a9a
72. 72
  Toda, N.; Asano, S.; Barbas, C. F. Angew. Chem., Int. Ed. 2013, 52, 12592
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  72
  Rapid, stable, chemoselective labeling of thiols with Julia-Kocienski-like reagents: A serum-stable alternative to maleimide-based protein conjugation
  Toda, Narihiro; Asano, Shigehiro; Barbas, Carlos F., III
  Angewandte Chemie, International Edition (2013), 52 (48), 12592-12596CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
  We have developed a class of sulfone derivs. for applications in protein conjugation chem., and we have compared the newly synthesized conjugates to maleimide conjugates. Methylsulfonyl-functionalized five-membered cyclic compds., such as phenyltetrazole or phenyloxadiazole, reacted rapidly and specifically with thiols in small mols. and proteins with exquisite chemoselectivity at biol. relevant pH values (pH 5.8 - 8.0). Designer heteroarom. sulfones allowed for the selective introduction of a fluorophore and poly(ethylene) glycol chains (PEGylation), and provided protein conjugates with superior stability compared to maleimide-conjugated proteins in human plasma. Given the speed, selectivity, and stability of the sulfone-cysteine reactions described herein, we anticipate that this "thiol-Click" approach will find broad application in peptide and protein chem. and for the development of antibody drug conjugates.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhs1Wms7%252FF&md5=ef91e1e933d116482b9e886c94c6cdd0
73. 73
  Patterson, J. T.; Asano, S.; Li, X.; Rader, C.; Barbas, C. F. Bioconjugate Chem. 2014, 25, 1402
  [ ACS Full Text ], [ CAS], Google Scholar
  73
  Improving the Serum Stability of Site-Specific Antibody Conjugates with Sulfone Linkers
  Patterson, James T.; Asano, Shigehiro; Li, Xiuling; Rader, Christoph; Barbas, Carlos F., III
  Bioconjugate Chemistry (2014), 25 (8), 1402-1407CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
  Current routes for synthesizing antibody-drug conjugates commonly rely on maleimide linkers to react with cysteine thiols. However, thioether exchange with metabolites and serum proteins can compromise conjugate stability and diminish in vivo efficacy. We report the application of a phenyloxadiazole sulfone linker for the prepn. of trastuzumab conjugates. This sulfone linker site-specifically labeled engineered cysteine residues in THIOMABs and improved antibody conjugate stability in human plasma at sites previously shown to be labile for maleimide conjugates. Similarly, sulfone conjugation with selenocysteine in an anti-ROR1 scFv-Fc improved human plasma stability relative to maleimide conjugation. Kinetically controlled labeling of a THIOMAB contg. two cysteine substitutions was also achieved, offering a strategy for producing antibody conjugates with expanded valency.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXht12gu77I&md5=1692372289fc0c7dabf1374851b5ccd6
74. 74
  Abbas, A.; Xing, B.; Loh, T.-P. Angew. Chem., Int. Ed. 2014, 53, 7491
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  74
  Allenamides as Orthogonal Handles for Selective Modification of Cysteine in Peptides and Proteins
  Abbas, Ata; Xing, Bengang; Loh, Teck-Peng
  Angewandte Chemie, International Edition (2014), 53 (29), 7491-7494CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
  In this study, a remarkably simple and direct strategy has been successfully developed to selectively label target cysteine residues in fully unprotected peptides and proteins. The strategy is based on the reaction between allenamides and the cysteine thiol, and proceeds swiftly in aq. medium with excellent selectivity and quant. conversion, thus forming a stable and irreversible conjugate. The combined simplicity and mildness of the process project allenamide as robust and versatile handles to target cysteines and has potential use in biol. systems. Addnl., fluorescent-labeling studies demonstrated that the installation of a C-terminal allenamide moiety onto various mols. of interest may supply a new methodol. towards the site-specific labeling of cysteine-contg. proteins. Such a new labeling strategy may thus open a window for its application in the field of life sciences.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXovVKltb0%253D&md5=bd00e8d70e768cf9a4b84422b2ee10ed
75. 75
  Lutolf, M. P.; Tirelli, N.; Cerritelli, S.; Cavalli, L.; Hubbell, J. A. Bioconjugate Chem. 2001, 12, 1051
  [ ACS Full Text ], [ CAS], Google Scholar
  75
  Systematic Modulation of Michael-Type Reactivity of Thiols through the Use of Charged Amino Acids
  Lutolf, M. P.; Tirelli, N.; Cerritelli, S.; Colussi, L.; Hubbell, J. A.
  Bioconjugate Chemistry (2001), 12 (6), 1051-1056CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
  A quant. structure-reactivity relationship for the Michael-type addn. of thiols onto acrylates was detd. Several thiol-contg. peptides were investigated by examg. the correlation between the second-order rate const. of their addn. onto PEG-diacrylate and the pKa of the thiols within a peptide. By introducing charged amino acids in close proximity to a cysteine, the pKa of the thiol was systematically modulated by electrostatic interactions. Pos. charges from the amino acid arginine decreased the pKa of the thiol and accelerated the reaction with acrylates while neg. charges from aspartic acids showed the opposite effect. A linear correlation between thiolate concns. and kinetic consts. was found, confirming the role of thiolates as the reactive species in this Michael-type reaction. The relevant factors influencing the reactivity were the sign and the no. of the neighboring charges, while the position of these charges had little effect on reactivity. These results provide a basis for the rational design of peptides, where the kinetics, and thus, selectivity of protein/peptide conjugation with polymeric structures via Michael-type addn. reactions can be controlled.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3MXmvFSgtr0%253D&md5=cb14139b26a0fdf4070841d9b2e383d5
76. 76
  Ma, F.-H.; Chen, J.-L.; Li, Q.-F.; Zuo, H.-H.; Huang, F.; Su, X.-C. Chem.—Asian J. 2014, 9, 1808
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  76
  Kinetic Assay of the Michael Addition-Like Thiol-Ene Reaction and Insight into Protein Bioconjugation
  Ma, Fei-He; Chen, Jia-Liang; Li, Qing-Feng; Zuo, Hui-Hui; Huang, Feng; Su, Xun-Cheng
  Chemistry - An Asian Journal (2014), 9 (7), 1808-1816CODEN: CAAJBI; ISSN:1861-4728. (Wiley-VCH Verlag GmbH & Co. KGaA)
  The chem. modification of proteins is a valuable technique in understanding the functions, interactions, and dynamics of proteins. Reactivity and selectivity are key issues in current chem. modification of proteins. The Michael addn.-like thiol-ene reaction is a useful tool that can be used to tag proteins with high selectivity for the solvent-exposed thiol groups of proteins. To obtain insight into the bioconjugation of proteins with this method, a kinetic anal. was performed. New vinyl-substituted pyridine derivs. were designed and synthesized. The reactivity of these vinyl tags with L-cysteine was evaluated by UV absorption and high-resoln. NMR spectroscopy. The results show that protonation of pyridine plays a key role in the overall reaction rates. The kinetic parameters were assessed in protein modification. The different reactivities of these vinyl tags with solvent-exposed cysteine is valuable information in the selective labeling of proteins with multiple functional groups.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXosV2gsro%253D&md5=e4878dfc5437061ec2b42f5098341589
77. 77
  Moody, P.; Chudasama, V.; Nathani, R. I.; Maruani, A.; Martin, S.; Smith, M. E. B.; Caddick, S. Chem. Commun. 2014, 50, 4898
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  77
  A rapid, site-selective and efficient route to the dual modification of DARPins
  Moody, Paul; Chudasama, Vijay; Nathani, Ramiz I.; Maruani, Antoine; Martin, Stephen; Smith, Mark E. B.; Caddick, Stephen
  Chemical Communications (Cambridge, United Kingdom) (2014), 50 (38), 4898-4900CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
  Designed ankyrin repeat proteins (DARPins) are valuable tools in both biochem. and medicine. Herein we describe a rapid, simple method for the dual modification of DARPins by introduction of cysteine mutations at specific positions that results in a vast difference in their thiol nucleophilicity, allowing for clean sequential modification.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXmtlertrg%253D&md5=d084af56b20d37e36f6e13b3eadace30
78. 78
  Shen, B.-Q.; Xu, K.; Liu, L.; Raab, H.; Bhakta, S.; Kenrick, M.; Parsons-Reponte, K. L.; Tien, J.; Yu, S.-F.; Mai, E.; Li, D.; Tibbitts, J.; Baudys, J.; Saad, O. M.; Scales, S. J.; McDonald, P. J.; Hass, P. E.; Eigenbrot, C.; Nguyen, T.; Solis, W. A.; Fuji, R. N.; Flagella, K. M.; Patel, D.; Spencer, S. D.; Khawli, L. A.; Ebens, A.; Wong, W. L.; Vandlen, R.; Kaur, S.; Sliwkowski, M. X.; Scheller, R. H.; Polakis, P.; Junutula, J. R. Nat. Biotechnol. 2012, 30, 184
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  78
  Conjugation site modulates the in vivo stability and therapeutic activity of antibody-drug conjugates
  Shen, Ben-Quan; Xu, Keyang; Liu, Luna; Raab, Helga; Bhakta, Sunil; Kenrick, Margaret; Parsons-Reponte, Kathryn L.; Tien, Janet; Yu, Shang-Fan; Mai, Elaine; Li, Dongwei; Tibbitts, Jay; Baudys, Jakub; Saad, Ola M.; Scales, Suzie J.; McDonald, Paul J.; Hass, Philip E.; Eigenbrot, Charles; Nguyen, Trung; Solis, Willy A.; Fuji, Reina N.; Flagella, Kelly M.; Patel, Darshana; Spencer, Susan D.; Khawli, Leslie A.; Ebens, Allen; Wong, Wai Lee; Vandlen, Richard; Kaur, Surinder; Sliwkowski, Mark X.; Scheller, Richard H.; Polakis, Paul; Junutula, Jagath R.
  Nature Biotechnology (2012), 30 (2), 184-189CODEN: NABIF9; ISSN:1087-0156. (Nature Publishing Group)
  The reactive thiol in cysteine is used for coupling maleimide linkers in the generation of antibody conjugates. To assess the impact of the conjugation site, we engineered cysteines into a therapeutic HER2/neu antibody at three sites differing in solvent accessibility and local charge. The highly solvent-accessible site rapidly lost conjugated thiol-reactive linkers in plasma owing to maleimide exchange with reactive thiols in albumin, free cysteine or glutathione. In contrast, a partially accessible site with a pos. charged environment promoted hydrolysis of the succinimide ring in the linker, thereby preventing this exchange reaction. The site with partial solvent-accessibility and neutral charge displayed both properties. In a mouse mammary tumor model, the stability and therapeutic activity of the antibody conjugate were affected pos. by succinimide ring hydrolysis and neg. by maleimide exchange with thiol-reactive constituents in plasma. Thus, the chem. and structural dynamics of the conjugation site can influence antibody conjugate performance by modulating the stability of the antibody-linker interface.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtVGqtLg%253D&md5=c647fc5bdfe93dfdabb15ca40934837f
79. 79
  (a) Valkevich, E. M.; Guenette, R. G.; Sanchez, N. A.; Chen, Y.-C.; Ge, Y.; Strieter, E. R. J. Am. Chem. Soc. 2012, 134, 6916
  [ ACS Full Text ], [ CAS], Google Scholar
  79a
  Forging Isopeptide Bonds Using Thiol-Ene Chemistry: Site-Specific Coupling of Ubiquitin Molecules for Studying the Activity of Isopeptidases
  Valkevich, Ellen M.; Guenette, Robert G.; Sanchez, Nicholas A.; Chen, Yi-chen; Ge, Ying; Strieter, Eric R.
  Journal of the American Chemical Society (2012), 134 (16), 6916-6919CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  Chem. methods for modifying proteins can enable studies aimed at uncovering biochem. function. Herein, we describe the use of thiol-ene coupling (TEC) chem. to report on the function of branched (also referred to as forked) ubiquitin trimers. We show how site-specific isopeptide (Nε-Gly-l-homothiaLys) bonds are forged between two mols. of Ub, demonstrating the power of TEC in protein conjugation. Moreover, we demonstrate that the Nε-Gly-l-homothiaLys isopeptide bond is processed to a similar extent by deubiquitinases (DUBs) as that of a native Nε-Gly-l-Lys isopeptide bond, thereby establishing the utility of TEC in the generation of Ub-Ub linkages. TEC is then applied to the synthesis of branched Ub trimers. Interrogation of these branched derivs. with DUBs reveals that the relative orientation of the two Ub units has a dramatic impact on how they are hydrolyzed. In particular, cleavage of K48C-linkages is suppressed when the central Ub unit is also conjugated through K6C, whereas cleavage proceeds normally when the central unit is conjugated through either K11C or K63C. The results of this work presage a role for branched polymeric Ub chains in regulating linkage-selective interactions.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xltl2hsb0%253D&md5=48a15faed42b65562a907de08f67bbdb
  (b) Li, F.; Allahverdi, A.; Yang, R.; Lua, G. B. J.; Zhang, X.; Cao, Y.; Korolev, N.; Nordenskiöld, L.; Liu, C.-F. Angew. Chem., Int. Ed. 2011, 50, 9611
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  79b
  A Direct Method for Site-Specific Protein Acetylation
  Li, Fupeng; Allahverdi, Abdollah; Yang, Renliang; Lua, Gavian Bing Jia; Zhang, Xiaohong; Cao, Yuan; Korolev, Nikolay; Nordenskioeld, Lars; Liu, Chuan-Fa
  Angewandte Chemie, International Edition (2011), 50 (41), 9611-9614, S9611/1-S9611/18CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
  A previously unexplored thiol-ene radical addn. reaction involving the com. available N-vinyl acetamide (NVA) is well suited for the S-acetamidoethylation of cysteine residues in synthetic peptides and recombinant proteins. The resultant N-acetyl-thialysine differs from natural acetyllysine only isosterically at the γ position of the amino acid structure and is functionally equiv. or similar to the latter. Although a limitation of the method is that the protein substrates should not contain other cysteines, it nevertheless has many potential applications, such as the histone epigenetic study--an intense research area at present. The reaction system is robust and gives near quant. yields of site-specifically acetylated proteins that can be purified in a simple chromatog. or dialysis step. The ease of implementation of this method also makes it easily adoptable for researchers from the bioscience research community. As such, this radical reaction approach provides a convenient enabling tool for the study of lysine acetylation biol. and will help to advance research in this important field.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhtFyls77K&md5=1a6488f091750257ec6519746d0010b3
80. 80
  Conte, M. L.; Staderini, S.; Marra, A.; Sánchez-Navarro, M.; Davis, B. G.; Dondoni, A. Chem. Commun. 2011, 47, 11086
  [ Crossref], [ PubMed], Google Scholar
  There is no corresponding record for this reference.
81. 81
  (a) Chen, S.; Touati, J.; Heinis, C. Chem. Commun. 2014, 50, 5267
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  81a
  Tracking chemical reactions on the surface of filamentous phage using mass spectrometry
  Chen, Shiyu; Touati, Jeremy; Heinis, Christian
  Chemical Communications (Cambridge, United Kingdom) (2014), 50 (40), 5267-5269CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
  Chem. modification of phage libraries has allowed the in vitro evolution of ligands having properties not provided by natural polypeptides. The development of novel and more diverse chem. reactions on phage was hampered by the lack of anal. methods to efficiently monitor the reaction products on the more than 10 000 kDa large filamentous phage particles. Herein, we present a strategy to detect chem. modified peptides on phage based on enzymic release of peptide from phage and mass spectrometry anal.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXmsFequrs%253D&md5=84bce15829da90551b84a6a8aec46dd5
  (b) Chen, S.; Bertoldo, D.; Angelini, A.; Pojer, F.; Heinis, C. Angew. Chem., Int. Ed. 2014, 53, 1602
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  81b
  Peptide Ligands Stabilized by Small Molecules
  Chen, Shiyu; Bertoldo, Davide; Angelini, Alessandro; Pojer, Florence; Heinis, Christian
  Angewandte Chemie, International Edition (2014), 53 (6), 1602-1606CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
  Bicyclic peptides generated through directed evolution by using phage display offer an attractive ligand format for the development of therapeutics. Being nearly 100-fold smaller than antibodies, they promise advantages such as access to chem. synthesis, efficient diffusion into tissues, and needle-free application. However, unlike antibodies, they do not have a folded structure in soln. and thus do not bind as well as antibodies. We developed bicyclic peptides with hydrophilic chem. structures at their center to promote noncovalent intramol. interactions, thereby stabilizing the peptide conformation. The sequences of the peptides isolated by phage display from large combinatorial libraries were strongly influenced by the type of small mol. used in the screen, thus suggesting that the peptides fold around the small mols. X-ray structure anal. revealed that the small mols. indeed formed hydrogen bonds with the peptides. These noncovalent interactions stabilize the peptide-protein complexes and contribute to the high binding affinity.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtVyltLc%253D&md5=4bc852345c54171bd8c7143a563bba2b
  (c) Angelini, A.; Diderich, P.; Morales-Sanfrutos, J.; Thurnheer, S.; Hacker, D.; Menin, L.; Heinis, C. Bioconjugate Chem. 2012, 23, 1856
  [ ACS Full Text ], [ CAS], Google Scholar
  81c
  Chemical Macrocyclization of Peptides Fused to Antibody Fc Fragments
  Angelini, Alessandro; Diderich, Philippe; Morales-Sanfrutos, Julia; Thurnheer, Sarah; Hacker, David; Menin, Laure; Heinis, Christian
  Bioconjugate Chemistry (2012), 23 (9), 1856-1863CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
  To extend the plasma half-life of a bicyclic peptide antagonist, we chose to link it to the Fc fragment of the long-lived serum protein IgG1. Instead of chem. conjugating the entire bicyclic peptide, we recombinantly expressed its peptide moiety as a fusion protein to an Fc fragment and subsequently cyclized the peptide by chem. reacting its three cysteine residues with tris-(bromomethyl)benzene. This reaction was efficient and selective, yielding completely modified peptide fusion protein and no side products. After optimization of the linker and the Fc fragment format, the bicyclic peptide was fully functional as an inhibitor (Ki = 76 nM) and showed an extended terminal half-life of 1.5 days in mice. The unexpectedly clean reaction makes chem. macrocyclization of peptide-Fc fusion proteins an attractive synthetic approach. Its good compatibility with the Fc fragment may lend the bromomethylbenzene-based chem. also for the generation of antibody-drug conjugates.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtVGntrrJ&md5=8b935079985721863d5833e472013824
  (d) Angelini, A.; Heinis, C. Curr. Opin. Chem. Biol. 2011, 15, 355
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  81d
  Post-translational modification of genetically encoded polypeptide libraries
  Angelini, Alessandro; Heinis, Christian
  Current Opinion in Chemical Biology (2011), 15 (3), 355-361CODEN: COCBF4; ISSN:1367-5931. (Elsevier B.V.)
  The genetic encoding of polypeptides with biol. display systems enables the facile generation and screening of very large combinatorial libraries of mols. By post-translationally modifying the encoded polypeptides, chem. and structurally more diverse mols. beyond linear amino acid polymers can be generated. The first post-translational modification applied to encoded polypeptides, the oxidn. of cysteine residues to form disulfide bridges, is a natural one and was used to cyclise short peptides soon after the invention of phage display. Recently a range of non-natural chem. strategies for the post-translational modification of encoded polypeptide repertoires were applied to generate optical biosensors, semisynthetic polypeptides, peptide-drug conjugates, redox-insensitive monocyclic peptides or multicyclic peptides, and these strategies are reviewed in this article.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXntV2lur0%253D&md5=e866df303755fc97722fc56344e8b1d7
  (e) Heinis, C.; Rutherford, T.; Freund, S.; Winter, G. Nat. Chem. Biol. 2009, 5, 502
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  81e
  Phage-encoded combinatorial chemical libraries based on bicyclic peptides
  Heinis, Christian; Rutherford, Trevor; Freund, Stephan; Winter, Greg
  Nature Chemical Biology (2009), 5 (7), 502-507CODEN: NCBABT; ISSN:1552-4450. (Nature Publishing Group)
  Here we describe a phage strategy for the selection of ligands based on bicyclic or linear peptides attached covalently to an org. core. We designed peptide repertoires with three reactive cysteine residues, each spaced apart by several random amino acid residues, and we fused the repertoires to the phage gene-3-protein. Conjugation with tris-(bromomethyl)benzene via the reactive cysteines generated repertoires of peptide conjugates with two peptide loops anchored to a mesitylene core. Iterative affinity selections yielded several enzyme inhibitors; after further mutagenesis and selection, we were able to chem. synthesize a lead inhibitor (PK15; Ki = 1.5 nM) specific to human plasma kallikrein that efficiently interrupted the intrinsic coagulation pathway in human plasma tested ex vivo. This approach offers a powerful means of generating and selecting bicyclic macrocycles (or if cleaved, linear derivs. thereof) as ligands poised at the interface of small-mol. drugs and biologics.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXms1altbs%253D&md5=0634460f77b185fbcf85309c6dbf93e3
82. 82
  Fukunaga, K.; Hatanaka, T.; Ito, Y.; Minami, M.; Taki, M. Chem. Commun. 2014, 50, 3921
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  82
  Construction of a crown ether-like supramolecular library by conjugation of genetically-encoded peptide linkers displayed on bacteriophage T7
  Fukunaga, Keisuke; Hatanaka, Takaaki; Ito, Yuji; Minami, Michiko; Taki, Masumi
  Chemical Communications (Cambridge, United Kingdom) (2014), 50 (30), 3921-3923CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
  By using the 10BASEd-T, the authors synthesized a crown ether-like macrocyclic library possessing randomized peptide linkers on bacteriophage T7. Among 1.5 × 109 diversities of the supramol. candidates, the authors have obtained a specific binder for the N-terminal domain of Hsp90.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXks1Srtbc%253D&md5=5ddeebf7fc041122e3fbbcb7ca233189
83. 83
  Bellotto, S.; Chen, S.; Rentero Rebollo, I.; Wegner, H. A.; Heinis, C. J. Am. Chem. Soc. 2014, 136, 5880
  [ ACS Full Text ], [ CAS], Google Scholar
  83
  Phage Selection of Photoswitchable Peptide Ligands
  Bellotto, Silvia; Chen, Shiyu; Rentero Rebollo, Inmaculada; Wegner, Hermann A.; Heinis, Christian
  Journal of the American Chemical Society (2014), 136 (16), 5880-5883CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  Photoswitchable ligands are powerful tools to control biol. processes at high spatial and temporal resoln. Unfortunately, such ligands exist only for a limited no. of proteins and their development by rational design is not trivial. We have developed an in vitro evolution strategy to generate light-activatable peptide ligands to targets of choice. In brief, random peptides were encoded by phage display, chem. cyclized with an azobenzene linker, exposed to UV light to switch the azobenzene into cis conformation, and panned against the model target streptavidin. Isolated peptides shared strong consensus sequences, indicating target-specific binding. Several peptides bound with high affinity when cyclized with the azobenzene linker, and their affinity could be modulated by UV light. The presented method is robust and can be applied for the in vitro evolution of photoswitchable ligands to virtually any target.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXls1Crsb4%253D&md5=28162c9cf4f3e0b367caea44b515276e
84. 84
  (a) Zou, Y.; Spokoyny, A. M.; Zhang, C.; Simon, M. D.; Yu, H.; Lin, Y.-S.; Pentelute, B. L. Org. Biomol. Chem. 2014, 12, 566
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  84a
  Convergent diversity-oriented side-chain macrocyclization scan for unprotected polypeptides
  Zou, Yekui; Spokoyny, Alexander M.; Zhang, Chi; Simon, Mark D.; Yu, Hongtao; Lin, Yu-Shan; Pentelute, Bradley L.
  Organic & Biomolecular Chemistry (2014), 12 (4), 566-573CODEN: OBCRAK; ISSN:1477-0520. (Royal Society of Chemistry)
  Here we describe a general synthetic platform for side-chain macrocyclization of an unprotected peptide library based on the SNAr reaction between cysteine thiolates and a new generation of highly reactive perfluoro-arom. small mol. linkers. This strategy enabled us to simultaneously "scan" two cysteine residues positioned from i, i + 1 to i, i + 14 sites in a polypeptide, producing 98 macrocyclic products from reactions of 14 peptides with 7 linkers. A complementary reverse strategy was developed; cysteine residues within the polypeptide were first modified with non-bridging perfluoroaryl moieties and then com. available dithiol linkers were used for macrocyclization. The highly convergent, site-independent, and modular nature of these two strategies coupled with the unique chemoselectivity of a SNAr transformation allows for the rapid diversity-oriented synthesis of hybrid macrocyclic peptide libraries with varied chem. and structural complexities.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhvFKhsbvF&md5=ae75e82db7691c038b604e5fd2a80f4a
  (b) Zhang, C.; Dai, P.; Spokoyny, A. M.; Pentelute, B. L. Org. Lett. 2014, 16, 3652
  [ ACS Full Text ], [ CAS], Google Scholar
  84b
  Enzyme-Catalyzed Macrocyclization of Long Unprotected Peptides
  Zhang, Chi; Dai, Peng; Spokoyny, Alexander M.; Pentelute, Bradley L.
  Organic Letters (2014), 16 (14), 3652-3655CODEN: ORLEF7; ISSN:1523-7052. (American Chemical Society)
  A glutathione S-transferase (GST) catalyzed macrocyclization reaction for peptides up to 40 amino acids in length is reported. GST catalyzes the selective SNAr reaction between an N-terminal glutathione (GSH, γ-Glu-Cys-Gly) tag and a C-terminal perfluoroaryl-modified cysteine on the same polypeptide chain. Cyclic peptides ranging from 9 to 24 residues were quant. produced within 2 h in aq. pH = 8 buffer at room temp. The reaction was highly selective for cyclization at the GSH tag, enabling the combination of GST-catalyzed ligation with native chem. ligation to generate a large 40-residue peptide macrocycle.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtFWjtLzJ&md5=ed8a6b70496b596a8fd509b30ffe3db9
  (c) Zhang, C.; Spokoyny, A. M.; Zou, Y.; Simon, M. D.; Pentelute, B. L. Angew. Chem., Int. Ed. 2013, 52, 14001
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  84c
  Enzymatic "Click" Ligation: Selective Cysteine Modification in Polypeptides Enabled by Promiscuous Glutathione S-Transferase
  Zhang, Chi; Spokoyny, Alexander M.; Zou, Yekui; Simon, Mark D.; Pentelute, Bradley L.
  Angewandte Chemie, International Edition (2013), 52 (52), 14001-14005CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
  Naturally occurring glutathione S-transferase (GST) was used to catalyze an efficient "click" ligation between polypeptides with an N-terminal glutathione sequence and biomols. or chem. probes contg. perfluorinated arom. groups. The site-specific modification of one cysteine residue was possible in the presence of other unprotected cysteine residues and reactive functional groups.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhslOlt77F&md5=447585b915fad3dfcdc56d58c5c2a8c7
85. 85
  Griffin, B. A.; Adams, S. R.; Tsien, R. Y. Science 1998, 281, 269
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  85
  Specific covalent labeling of recombinant protein molecules inside live cells
  Griffin, B. Albert; Adams, Stephen R.; Tsein, Roger Y.
  Science (Washington, D. C.) (1998), 281 (5374), 269-272CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)
  Recombinant proteins contg. four cysteines at the i, i + 1, i + 4, and i + 5 positions of a α helix were fluorescently labeled in living cells by extracellular administration of 4',5'-bis(1,3,2-dithioarsolan-2-yl)fluorescein. This designed small ligand is membrane-permeant and nonfluorescent until it binds with high affinity and specificity to the tetracysteine domain. Such in situ labeling adds much less mass than does green fluorescent protein and offers greater versatility in attachment sites as well as potential spectroscopic and chem. properties. This system provides a recipe for slightly modifying a target protein so that it can be singled out from the many other proteins inside live cells and fluorescently stained by small nonfluorescent dye mols. added from outside the cells.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK1cXksFKgs78%253D&md5=3d9867443016af9eb20745ed39b578a1
86. 86
  Kim, T. H.; Swierczewska, M.; Oh, Y.; Kim, A.; Jo, D. G.; Park, J. H.; Byun, Y.; Sadegh-Nasseri, S.; Pomper, M. G.; Lee, K. C.; Lee, S. Angew. Chem., Int. Ed. 2013, 52, 6880
  [ Crossref], [ CAS], Google Scholar
  86
  Mix to Validate: A Facile, Reversible PEGylation for Fast Screening of Potential Therapeutic Proteins In Vivo
  Kim, Tae Hyung; Swierczewska, Magdalena; Oh, Yumin; Kim, Ae Ryon; Jo, Dong Gyu; Park, Jae Hyung; Byun, Youngro; Sadegh-Nasseri, Scheherazade; Pomper, Martin G.; Lee, Kang Choon; Lee, Seulki
  Angewandte Chemie, International Edition (2013), 52 (27), 6880-6884CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
  The authors introduce a facile technique that allows for efficacy testing of protein drugs in animal models by extending the half-life in the blood of any selected protein candidate without compromising bioactivity. This technique offers the benefits of site-specific PEGylation without time-consuming and costly chem. modification and purifn. processes, enabling high-throughput testing of protein drugs in vivo. The general concept used is to PEGylate proteins through a complementary interaction between an oligo-histidine tag (His-tag) and a Ni2+ complex of nitrilotriacetic acid (NTA), which is now widely used in protein research. For example, protein immobilization techniques and protein labeling with fluorophores use the properties of a His-tag binding to NTA. The tumor necrosis factor-related apoptosis inducing ligand (TRAIL) was chosen as a model protein drug. The general design of reactive Ni-NTA-PEG analogs, and its binding to a His-tag, hexahistidine (H6), and fused protein are illustrated. Using TRAIL as a model protein, we demonstrated that a unique Ni-NTA-PEG analog assocd. with a His-tagged protein is able to provide outstanding physicochem. stability without compromising the bioactivity. Importantly, the Ni-NTA-PEG analog maximized the pharmacol. efficacy of the protein drug in vivo.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXptVantbo%253D&md5=9be70b55fc73724485eb58f41dfd3a92
87. 87
  (a) Rashidian, M.; Dozier, J. K.; Distefano, M. D. Bioconjugate Chem. 2013, 24, 1277
  [ ACS Full Text ], [ CAS], Google Scholar
  87a
  Enzymatic Labeling of Proteins: Techniques and Approaches
  Rashidian, Mohammad; Dozier, Jonathan K.; Distefano, Mark D.
  Bioconjugate Chemistry (2013), 24 (8), 1277-1294CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
  A review. Site-specific modification of proteins is a major challenge in modern chem. biol. due to the large no. of reactive functional groups typically present in polypeptides. Because of its importance in biol. and medicine, the development of methods for site-specific modification of proteins is an area of intense research. Selective protein modification procedures have been useful for oriented protein immobilization, for studies of naturally occurring post-translational modifications, for creating antibody-drug conjugates, for the introduction of fluorophores and other small mols. on to proteins, for examg. protein structure, folding, dynamics, and protein-protein interactions, and for the prepn. of protein-polymer conjugates. One of the most important approaches for protein labeling is to incorporate bioorthogonal functionalities into proteins at specific sites via enzymic reactions. The incorporated tags then enable reactions that are chemoselective, whose functional groups not only are inert in biol. media, but also do not occur natively in proteins or other macromols. This review article summarizes the enzymic strategies, which enable site-specific functionalization of proteins with a variety of different functional groups. The enzymes covered in this review include formylglycine generating enzyme, sialyltransferases, phosphopantetheinyltransferases, O-GlcNAc post-translational modification, sortagging, transglutaminase, farnesyltransferase, biotin ligase, lipoic acid ligase, and N-myristoyltransferase.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtVKku77P&md5=4197395b3554983f91f4eade70197dbe
  (b) Rashidian, M.; Kumarapperuma, S. C.; Gabrielse, K.; Fegan, A.; Wagner, C. R.; Distefano, M. D. J. Am. Chem. Soc. 2013, 135, 16388
  [ ACS Full Text ], [ CAS], Google Scholar
  87b
  Simultaneous Dual Protein Labeling Using a Triorthogonal Reagent
  Rashidian, Mohammad; Kumarapperuma, Sidath C.; Gabrielse, Kari; Fegan, Adrian; Wagner, Carston R.; Distefano, Mark D.
  Journal of the American Chemical Society (2013), 135 (44), 16388-16396CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  Construction of heterofunctional proteins is a rapidly emerging area of biotherapeutics. Combining a protein with other moieties, such as a targeting element, a toxic protein or small mol., and a fluorophore or polyethylene glycol (PEG) group, can improve the specificity, functionality, potency, and pharmacokinetic profile of a protein. Protein farnesyl transferase (PFTase) is able to site-specifically and quant. prenylate proteins contg. a C-terminal CaaX-box amino acid sequence with various modified isoprenoids. Here, the authors describe the design, synthesis, and application of a triorthogonal reagent (I) that can be used to site-specifically incorporate an alkyne and aldehyde group simultaneously into a protein. To illustrate the capabilities of this approach, a protein was enzymically modified with compd. I followed by oxime ligation and click reaction to simultaneously incorporate an azido-tetramethylrhodamine (TAMRA) fluorophore and an aminooxy-PEG moiety. This was performed with both a model protein [green fluorescent protein (GFP)] as well as a therapeutically useful protein [ciliary neurotrophic factor (CNTF)]. Next, a protein was enzymically modified with compd. I followed by coupling to an azido-bis-methotrexate dimerizer and aminooxy-TAMRA. Incubation of that construct with a dihydrofolate reductase (DHFR)-DHFR-anti-CD3 fusion protein resulted in the self-assembly of nanoring structures that were endocytosed into T-leukemia cells and visualized therein. These results highlight how complex multifunctional protein assemblies can be prepd. using this facile triorthogonal approach.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhs1CktLbK&md5=882648fafd4196fe3c6c590862d7e496
88. 88
  Uchinomiya, S.; Ojida, A.; Hamachi, I. Inorg. Chem. 2014, 53, 1816
  [ ACS Full Text ], [ CAS], Google Scholar
  88
  Peptide Tag/Probe Pairs Based on the Coordination Chemistry for Protein Labeling
  Uchinomiya, Shohei; Ojida, Akio; Hamachi, Itaru
  Inorganic Chemistry (2014), 53 (4), 1816-1823CODEN: INOCAJ; ISSN:0020-1669. (American Chemical Society)
  A review. Protein-labeling methods serve as essential tools for analyzing functions of proteins of interest under complicated biol. conditions such as in live cells. These labeling methods are useful not only to fluorescently visualize proteins of interest in biol. systems but also to conduct protein and cell analyses by harnessing the unique functions of mol. probes. Among the various labeling methods available, an appropriate binding pair consisting of a short peptide and a de novo designed small mol. probe has attracted attention because of its wide utility and versatility. Most peptide tag/probe pairs exploit metal-ligand coordination interactions as the main binding force responsible for their assocn. Herein, the authors provide an overview of the recent progress of these coordination-chem.-based protein-labeling methods and their applications for fluorescence imaging and functional anal. of cellular proteins, while highlighting the authors' originally developed labeling methods. These successful examples clearly exemplify the utility and versatility of metal coordination chem. in protein functional anal.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhs1Wlt7nF&md5=6ba4ee9432b0acb842b3f7629f0b6474
89. 89
  (a) Chen, X.-H.; Xiang, Z.; Hu, Y. S.; Lacey, V. K.; Cang, H.; Wang, L. ACS Chem. Biol. 2014, 9, 1956
  [ ACS Full Text ], [ CAS], Google Scholar
  89a
  Genetically Encoding an Electrophilic Amino Acid for Protein Stapling and Covalent Binding to Native Receptors
  Chen, Xiao-Hua; Xiang, Zheng; Hu, Ying S.; Lacey, Vanessa K.; Cang, Hu; Wang, Lei
  ACS Chemical Biology (2014), 9 (9), 1956-1961CODEN: ACBCCT; ISSN:1554-8929. (American Chemical Society)
  Covalent bonds can be generated within and between proteins by an unnatural amino acid (Uaa) reacting with a natural residue through proximity-enabled bioreactivity. Until now, Uaas have been developed to react mainly with cysteine in proteins. Here the authors genetically encoded an electrophilic Uaa capable of reacting with histidine and lysine, thereby expanding the diversity of target proteins and the scope of the proximity-enabled protein crosslinking technol. In addn. to efficient crosslinking of proteins inter- and intramolecularly, this Uaa permits direct stapling of a protein α-helix in a recombinant manner and covalent binding of native membrane receptors in live cells. The target diversity, recombinant stapling, and covalent targeting of endogenous proteins enabled by this versatile Uaa should prove valuable in developing novel research tools, biol. diagnostics, and therapeutics by exploiting covalent protein linkages for specificity, irreversibility, and stability.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtFeisbrE&md5=4938b2a7b1f9e72d050811a5e5ed0bc0
  (b) Furman, J. L.; Kang, M.; Choi, S.; Cao, Y.; Wold, E. D.; Sun, S. B.; Smider, V. V.; Schultz, P. G.; Kim, C. H. J. Am. Chem. Soc. 2014, 136, 8411
  [ ACS Full Text ], [ CAS], Google Scholar
  89b
  A Genetically Encoded aza-Michael Acceptor for Covalent Cross-Linking of Protein-Receptor Complexes
  Furman, Jennifer L.; Kang, Mingchao; Choi, Seihyun; Cao, Yu; Wold, Erik D.; Sun, Sophie B.; Smider, Vaughn V.; Schultz, Peter G.; Kim, Chan Hyuk
  Journal of the American Chemical Society (2014), 136 (23), 8411-8417CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  Selective covalent bond formation at a protein-protein interface potentially can be achieved by genetically introducing into a protein an appropriately "tuned" electrophilic unnatural amino acid that reacts with a native nucleophilic residue in its cognate receptor upon complex formation. We have evolved orthogonal aminoacyl-tRNA synthetase/tRNACUA pairs that genetically encode three aza-Michael acceptor amino acids, Nε-acryloyl-(S)-lysine (AcrK, 1), p-acrylamido-(S)-phenylalanine (AcrF, 2), and p-vinylsulfonamido-(S)-phenylalanine (VSF, 3), in response to the amber stop codon in Escherichia coli. Using an αErbB2 Fab-ErbB2 antibody-receptor pair as an example, we demonstrate covalent bond formation between an αErbB2-VSF mutant and a sp. surface lysine ε-amino group of ErbB2, leading to near quant. crosslinking to either purified ErbB2 in vitro or to native cellular ErbB2 at physiol. pH. This efficient biocompatible reaction may be useful for creating novel cell biol. probes, diagnostics, or therapeutics that selectively and irreversibly bind a target protein in vitro or in living cells.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXosVSqtbc%253D&md5=bfd340b02d54ec4367b4785f2a49633c
  (c) Lu, Y.; Huang, F.; Wang, J.; Xia, J. Bioconjugate Chem. 2014, 25, 989
  [ ACS Full Text ], [ CAS], Google Scholar
  89c
  Affinity-Guided Covalent Conjugation Reactions Based on PDZ-Peptide and SH3-Peptide Interactions
  Lu, Yao; Huang, Feng; Wang, Jianpeng; Xia, Jiang
  Bioconjugate Chemistry (2014), 25 (5), 989-999CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
  Specific protein-peptide interactions are prevalent in the living cells and form a tightly regulated signaling network. These interactions, many of which have structural information revealed, provide ideal templates for affinity-guided covalent bioconjugation. Here we report the development of a set of four new reactions that covalently and site-specifically link nonenzymic scaffolding domains (two PDZ and two SH3 domains) and their ligands through thiol-chloroacetyl SN2 reaction. Guided by the three-dimensional structure of the wild type complex, a selected position of the protein was mutated to cysteine, and at the same time, an α-chloroacetyl group was installed at a corresponding position of the peptide. Specific binding interaction between the two brings the reactive groups into close proximity, converts the nonreactive cysteine residue into a content-dependent reactive site, and induces the nucleophilic reaction that is inert in the absence of the binding event. The specificity, orthogonality, and modularity of the four reactions were characterized, the reaction was applied to label proteins in vitro and receptor on the surface of mammalian cells, and the system was utilized to assemble covalent protein complexes with unnatural geometries.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXmt1Gjt7o%253D&md5=56257c8fa44ec69c3df3587178bad393
  (d) Xiang, Z.; Lacey, V. K.; Ren, H.; Xu, J.; Burban, D. J.; Jennings, P. A.; Wang, L. Angew. Chem., Int. Ed. 2014, 53, 2190
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  89d
  Proximity-Enabled Protein Crosslinking through Genetically Encoding Haloalkane Unnatural Amino Acids
  Xiang, Zheng; Lacey, Vanessa K.; Ren, Haiyan; Xu, Jing; Burban, David J.; Jennings, Patricia A.; Wang, Lei
  Angewandte Chemie, International Edition (2014), 53 (8), 2190-2193CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
  The selective generation of covalent bonds between and within proteins would provide new avenues for studying protein function and engineering proteins with new properties. New covalent bonds were genetically introduced into proteins by enabling an unnatural amino acid (Uaa) to selectively react with a proximal natural residue. This proximity-enabled bioreactivity was expanded to a series of haloalkane Uaas. Orthogonal tRNA/synthetase pairs were evolved to incorporate these Uaas, which only form a covalent thioether bond with cysteine when positioned in close proximity. By using the Uaa and cysteine, spontaneous covalent bond formation was demonstrated between an affibody and its substrate Z protein, thereby leading to irreversible binding, and within the affibody to increase its thermostability. This strategy of proximity-enabled protein crosslinking (PEPC) may be generally expanded to target different natural amino acids, thus providing diversity and flexibility in covalent bond formation for protein research and protein engineering.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtVygurk%253D&md5=e6e50075baae0dcf7fbdab1b64287bf3
  (e) Masuya, T.; Murai, M.; Ifuku, K.; Morisaka, H.; Miyoshi, H. Biochemistry 2014, 53, 2307
  [ ACS Full Text ], [ CAS], Google Scholar
  89e
  Site-Specific Chemical Labeling of Mitochondrial Respiratory Complex I through Ligand-Directed Tosylate Chemistry
  Masuya, Takahiro; Murai, Masatoshi; Ifuku, Kentaro; Morisaka, Hironobu; Miyoshi, Hideto
  Biochemistry (2014), 53 (14), 2307-2317CODEN: BICHAW; ISSN:0006-2960. (American Chemical Society)
  The site-specific chem. modification of NADH-quinone oxidoreductase (complex I) by various functional probes such as fluorophores and microbeads, without affecting the enzyme activity, may allow single-mol. analyses of putative dynamic conformational changes in the enzyme. In an attempt to address this challenge, we performed site-specific alkynylation of complex I in bovine heart submitochondrial particles by means of a ligand-directed tosylate (LDT) chem. strategy with synthetic acetogenin ligand 1, which has an alkynylated tosylate in the tail moiety, as a high-affinity ligand against the enzyme. The terminal alkyne was chosen as the tag to be incorporated into the enzyme because this functional group can serve as a "footing" for subsequent diverse chem. modifications via so-called click chem. (i.e., azide-alkyne [3+2] cycloaddn. in water). To identify the position alkynylated by ligand 1, fluorescent tetramethylrhodamine was covalently attached to the incorporated alkyne by click chem. after the solubilization of complex I. Detailed proteomic analyses revealed that alkynylation occurred at Asp160 in the 49 kDa subunit, which may be located in the inner part of the putative quinone-binding cavity. The alkynylation was completely suppressed in the presence of an excess of other inhibitors such as bullatacin and quinazoline. While the reaction yield of the alkynylation step via LDT chem. was estd. to be ∼50%, the alkynylation unfortunately resulted in the almost complete inhibition of enzyme activity. Nevertheless, the results of this study demonstrate that complex I can be site-specifically alkynylated through LDT chem., providing a clue about the diverse chem. modifications of the enzyme in combination with click chem.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXks1yrsb8%253D&md5=c9c119588420607931bc99947e802247
  (f) Hayashi, T.; Sun, Y.; Tamura, T.; Kuwata, K.; Song, Z.; Takaoka, Y.; Hamachi, I. J. Am. Chem. Soc. 2013, 135, 12252
  [ ACS Full Text ], [ CAS], Google Scholar
  89f
  Semisynthetic Lectin-4-Dimethylaminopyridine Conjugates for Labeling and Profiling Glycoproteins on Live Cell Surfaces
  Hayashi, Takahiro; Sun, Yedi; Tamura, Tomonori; Kuwata, Keiko; Song, Zhining; Takaoka, Yousuke; Hamachi, Itaru
  Journal of the American Chemical Society (2013), 135 (33), 12252-12258CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  Glycoproteins on cell surfaces play important roles in biol. processes, including cell-cell interaction/signaling, immune response, and cell differentiation. Given the diversity of the structure of glycans, labeling and imaging of selected glycoproteins are challenging, although several promising strategies have been developed recently. Here, we design and construct semisynthetic reactive lectins (sugar-binding proteins) that are able to selectively label glycoproteins. Congerin II, an animal galectin, and wheat germ agglutinin are conjugated with 4-dimethylaminopyridine (DMAP), a well-known acyl transfer catalyst by our affinity-guided DMAP method and Cu(I)-assisted click chem. Selective labeling of glycoproteins is facilitated by the DMAP-tethered lectin catalysts both in vitro and on living cells. Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) anal. enabled us to isolate labeled glycoproteins that are uniquely exposed on distinct cell lines. Furthermore, the combination of immunopptn. with mass spectrometry (MS)-fingerprinting techniques allowed us to characterize 48 glycoproteins endogenously expressed on HeLa cells, and some low-abundant glycoproteins, such as epidermal growth factor receptor (EGFR) and neuropilin-1, were successfully identified. Our results demonstrate that semisynthetic DMAP-tethered lectins provide a new tool for labeling and profiling glycoproteins on living cells.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtFOltrjN&md5=87a7d74c4cfa15e0918b2aaa2b4bf2f3
  (g) Uchinomiya, S.; Nonaka, H.; Wakayama, S.; Ojida, A.; Hamachi, I. Chem. Commun. 2013, 49, 5022
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  89g
  In-cell covalent labeling of reactive His-tag fused proteins
  Uchinomiya, Shohei; Nonaka, Hiroshi; Wakayama, Sho; Ojida, Akio; Hamachi, Itaru
  Chemical Communications (Cambridge, United Kingdom) (2013), 49 (44), 5022-5024CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
  A new method for in-cell protein labeling was developed. This method employed a binding-induced nucleophilic reaction between the Cys-appended His-tag and the Ni(II)-NTA contg. an α-chloroacetamide. Using this method, not only labeling of His-tag fused proteins but also the detection of a protein-protein interaction was achieved inside living cells.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXntlaisrc%253D&md5=c1e81acd59aa9ecff7d3b41ed7abb5ec
  (h) Tamura, T.; Tsukiji, S.; Hamachi, I. J. Am. Chem. Soc. 2012, 134, 2216
  [ ACS Full Text ], [ CAS], Google Scholar
  89h
  Native FKBP12 Engineering by Ligand-Directed Tosyl Chemistry: Labeling Properties and Application to Photo-Cross-Linking of Protein Complexes in Vitro and in Living Cells
  Tamura, Tomonori; Tsukiji, Shinya; Hamachi, Itaru
  Journal of the American Chemical Society (2012), 134 (4), 2216-2226CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  The ability to modify target native (endogenous) proteins selectively in living cells with synthetic mols. should provide powerful tools for chem. biol. To this end, the authors recently developed a novel protein labeling technique termed ligand-directed tosyl (LDT) chem. This method uses labeling reagents in which a protein ligand and a synthetic probe are connected by a tosylate ester group. The authors previously demonstrated its applicability to the selective chem. labeling of several native proteins in living cells and mice. However, many fundamental features of this chem. remain to be studied. In this work, the authors investigated the relation between the LDT reagent structure and labeling properties by using native FK506-binding protein 12 (FKBP12) as a target protein. In vitro expts. revealed that the length and rigidity of the spacer structure linking the protein ligand and the tosylate group have significant effects on the overall labeling yield and labeling site. In addn. to histidine, which the authors reported previously, tyrosine and glutamate residues were identified as amino acids that are modified by LDT-mediated labeling. Through the screening of various spacer structures, piperazine was optimal for FKBP12 labeling in terms of labeling efficiency and site specificity. Using a piperazine-based LDT reagent contg. a photoreactive probe, the authors successfully demonstrated the labeling and UV-induced covalent crosslinking of FKBP12 and its interacting proteins in vitro and in living cells. This study not only furthers the understanding of the basic reaction properties of LDT chem. but also extends the applicability of this method to the investigation of biol. processes in mammalian cells.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XivVWrsg%253D%253D&md5=928d74d5f63d2be4a9b2b40baf7b5982
  (i) Fujishima, S.-h.; Yasui, R.; Miki, T.; Ojida, A.; Hamachi, I. J. Am. Chem. Soc. 2012, 134, 3961
  [ ACS Full Text ], [ CAS], Google Scholar
  89i
  Ligand-Directed Acyl Imidazole Chemistry for Labeling of Membrane-Bound Proteins on Live Cells
  Fujishima, Sho-hei; Yasui, Ryosuke; Miki, Takayuki; Ojida, Akio; Hamachi, Itaru
  Journal of the American Chemical Society (2012), 134 (9), 3961-3964CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  Chem.-based protein labeling in living cells is undoubtedly useful for understanding natural protein functions and for biol./pharmaceutical applications. Here, the authors report a novel approach for endogenous membrane-bound protein labeling for both in vitro and live cell conditions. A moderately reactive alkyloxyacyl imidazole (AI) assisted by ligand-binding affinity (ligand-directed AI (LDAI)) chem. allowed the authors to selectively modify natural proteins, such as dihydrofolate reductase (DHFR) and folate receptor (FR), neither of which could be efficiently labeled using the recently developed ligand-directed tosylate approach. It was clear that LDAI selectively labeled a single Lys(K32) in DHFR, proximal to the ligand-binding pocket. The authors also demonstrate that the fluorescein-labeled (endogenous, by LDAI) FR works as a fluorescent biosensor on the live KB cell surface, which allowed the authors to carry out unprecedented in situ kinetic anal. of ligand binding to FR.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XislSqu7w%253D&md5=6ccb65da77cad1b62892b738f42e1c55
  (j) Wang, H.; Koshi, Y.; Minato, D.; Nonaka, H.; Kiyonaka, S.; Mori, Y.; Tsukiji, S.; Hamachi, I. J. Am. Chem. Soc. 2011, 133, 12220
  [ ACS Full Text ], [ CAS], Google Scholar
  89j
  Chemical Cell-Surface Receptor Engineering Using Affinity-Guided, Multivalent Organocatalysts
  Wang, Hangxiang; Koshi, Yoichiro; Minato, Daishiro; Nonaka, Hiroshi; Kiyonaka, Shigeki; Mori, Yasuo; Tsukiji, Shinya; Hamachi, Itaru
  Journal of the American Chemical Society (2011), 133 (31), 12220-12228CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  Catalysts hold promise as tools for chem. protein modification. However, the application of catalysts or catalyst-mediated reactions to proteins has only recently begun to be addressed, mainly in in vitro systems. By radically improving the affinity-guided DMAP (4-dimethylaminopyridine) (AGD) catalysts that the authors previously reported, here the authors have developed a new organocatalyst-based approach that allows specific chem. acylation of a receptor protein on the surface of live cells. The catalysts consist of a set of multivalent DMAP groups (the acyl transfer catalyst) fused to a ligand specific to the target protein. It was clearly demonstrated by in vitro expts. that the catalyst multivalency enables remarkable enhancement of protein acylation efficiency in the labeling of three different proteins: congerin II, a Src homol. 2 (SH2) domain, and FKBP12. Using a multivalent AGD catalyst and optimized acyl donors contg. a chosen probe, the authors successfully achieved selective chem. labeling of bradykinin B2 receptor (B2R), a G-protein coupled receptor, on the live cell-surface. Furthermore, the present tool allowed the authors to construct a membrane protein (B2R)-based fluorescent biosensor, the fluorescence of which is enhanced (tuned on) in response to the antagonist ligand binding. The biosensor should be applicable to rapid and quant. screening and assay of potent drug candidates in the cellular context. The design concept of the affinity-guided, multivalent catalysts should facilitate further development of diverse catalyst-based protein modification tools, providing new opportunities for org. chem. in biol. research.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXptVSksLs%253D&md5=870e8766a9ab6216298c91a01586e022
  (k) Tsukiji, S.; Miyagawa, M.; Takaoka, Y.; Tamura, T.; Hamachi, I. Nat. Chem. Biol. 2009, 5, 341
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  89k
  Ligand-directed tosyl chemistry for protein labeling in vivo
  Tsukiji, Shinya; Miyagawa, Masayoshi; Takaoka, Yousuke; Tamura, Tomonori; Hamachi, Itaru
  Nature Chemical Biology (2009), 5 (5), 341-343CODEN: NCBABT; ISSN:1552-4450. (Nature Publishing Group)
  Here the authors describe a method for the site-selective attachment of synthetic mols. into specific 'endogenous' proteins in vivo using ligand-directed tosyl (LDT) chem. This approach was applied not only for chem. labeling proteins in living cells, tissues and mice but also for constructing a biosensor directly inside cells without genetic engineering. These data establish LDT chem. as a new tool for the study and manipulation of biol. systems.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXjsl2gurY%253D&md5=604943938355591f1f4f5e861c6a8278
  (l) Koshi, Y.; Nakata, E.; Miyagawa, M.; Tsukiji, S.; Ogawa, T.; Hamachi, I. J. Am. Chem. Soc. 2008, 130, 245
  [ ACS Full Text ], [ CAS], Google Scholar
  89l
  Target-Specific Chemical Acylation of Lectins by Ligand-Tethered DMAP Catalysts
  Koshi, Yoichiro; Nakata, Eiji; Miyagawa, Masayoshi; Tsukiji, Shinya; Ogawa, Tomohisa; Hamachi, Itaru
  Journal of the American Chemical Society (2008), 130 (1), 245-251CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  Because sugar-binding proteins, so-called lectins, play important roles in many biol. phenomena, the lectin-selective labeling should be useful for investigating biol. processes involving lectins as well as providing mol. tools for anal. of saccharides and these derivs. The authors describe herein a new strategy for lectin-selective labeling based on an acyl transfer reaction directed by ligand-tethered DMAP (4-dimethylaminopyridine). DMAP is an effective acyl transfer catalyst, which can activate an acyl ester for its transfer to a nucleophilic residue. To direct the acyl transfer reaction to a lectin of interest, the authors attached the DMAP to a saccharide ligand specific for the target lectin. It was clearly demonstrated by biochem. analyses that the target-selective labeling of Congerin II, an animal lectin having selective affinity for Lactose/LacNAc (N-acetyllactosamine), was achieved in the presence of Lac-tethered DMAPs and acyl donors contg. probes such as fluorescent mols. or biotin. Conventional peptide mapping expts. using HPLC and tandem mass-mass anal. revealed that the acyl transfer reaction site-specifically occurred at Tyr 51 of Cong II. This strategy was successfully extended to other lectins by changing the ligand part of the ligand-tethered DMAP. The authors also demonstrated that this labeling method is applicable not only to purified lectin in test tubes, but also to crude mixts. such as E. coli lysates or homogenized animal tissue samples expressing Congerin.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXhsVWqsLrK&md5=6e4b0361d59a53f2fef1724f78091821
90. 90
  Lodge, J. M.; Justin Rettenmaier, T.; Wells, J. A.; Pomerantz, W. C.; Mapp, A. K. MedChemComm 2014, 5, 370
  [ Crossref], [ CAS], Google Scholar
  90
  FP tethering: a screening technique to rapidly identify compounds that disrupt protein-protein interactions
  Lodge, Jean M.; Justin Rettenmaier, T.; Wells, James A.; Pomerantz, William C.; Mapp, Anna K.
  MedChemComm (2014), 5 (3), 370-375CODEN: MCCEAY; ISSN:2040-2503. (Royal Society of Chemistry)
  Tethering is a screening technique for discovering small-mol. fragments that bind to pre-detd. sites via formation of a disulfide bond. Tethering screens traditionally rely upon mass spectrometry to detect disulfide bond formation, which requires a time-consuming liq. chromatog. step. Here we show that tethering can be performed rapidly and inexpensively using a homogenous fluorescence polarization (FP) assay that detects displacement of a peptide ligand from the protein target as an indirect readout of disulfide formation. We apply this method, termed FP tethering, to identify fragments that disrupt the protein-protein interaction between the KIX domain of the transcriptional coactivator CBP and the transcriptional activator peptide pKID.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXjt1ymtbs%253D&md5=96da00435d8e4d5d16e53e7c67e7b41c
91. 91
  Sato, S.; Nakamura, H. Angew. Chem., Int. Ed. 2013, 52, 8681
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  91
  Ligand-Directed Selective Protein Modification Based on Local Single-Electron Transfer Catalysis
  Sato, Shinichi; Nakamura, Hiroyuki
  Angewandte Chemie, International Edition (2013), 52 (33), 8681-8684CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
  A photocatalyst ([Ru(bpy)3]2+) bound to a protein ligand was essential for the title method. Local single-electron transfer from the catalyst resulted in the formation of tyrosyl radicals. N'-Acetyl-N,N-dimethyl-1,4-phenylenediamine was used as the tyrosyl radical trapping agent and used in a radical addn. to afford selective modification of the target protein.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtVGrtrzK&md5=d72e4e5fc6db1c3da367a97a31563b2b
92. 92
  Brocchini, S.; Godwin, A.; Balan, S.; Choi, J.-W.; Zloh, M.; Shaunak, S. Adv. Drug Delivery Rev. 2008, 60, 3
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  92
  Disulfide bridge based PEGylation of proteins
  Brocchini, Steve; Godwin, Antony; Balan, Sibu; Choi, Ji-won; Zloh, Mire; Shaunak, Sunil
  Advanced Drug Delivery Reviews (2008), 60 (1), 3-12CODEN: ADDREP; ISSN:0169-409X. (Elsevier B.V.)
  A review. PEGylation is a clin. proven strategy for increasing the therapeutic efficacy of protein-based medicines. Our approach to site-specific PEGylation exploits the thiol selective chem. of the two cysteine sulfur atoms from an accessible disulfide. It involves two key steps: (1) disulfide redn. to release the two cystine thiols, and (2) bis-alkylation to give a three-carbon bridge to which PEG is covalently attached. During this process, irreversible denaturation of the protein does not occur. Mechanistically, the conjugation is conducted by a sequential, interactive bis-alkylation using α,β-unsatd.-β'-mono-sulfone functionalized PEG reagents. The combination of: - (a) maintaining the protein's tertiary structure after redn. of a disulfide, (b) bis-thiol selectivity of the PEG reagent, and (c) PEG assocd. steric shielding ensure that only one PEG mol. is conjugated at each disulfide. Our studies have shown that peptides, proteins, enzymes and antibody fragments can be site-specifically PEGylated using a native and accessible disulfide without destroying the mols.' tertiary structure or abolishing its biol. activity. As the stoichiometric efficiency of our approach also enables recycling of any unreacted protein, it offers the potential to make PEGylated biopharmaceuticals as cost-effective medicines.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXhtlyit7vP&md5=7b88a509897ed35ab3a8cc1b1609f271
93. 93
  (a) Badescu, G.; Bryant, P.; Bird, M.; Henseleit, K.; Swierkosz, J.; Parekh, V.; Tommasi, R.; Pawlisz, E.; Jurlewicz, K.; Farys, M.; Camper, N.; Sheng, X.; Fisher, M.; Grygorash, R.; Kyle, A.; Abhilash, A.; Frigerio, M.; Edwards, J.; Godwin, A. Bioconjugate Chem. 2014, 25, 1124
  [ ACS Full Text ], [ CAS], Google Scholar
  93a
  Bridging Disulfides for Stable and Defined Antibody Drug Conjugates
  Badescu, George; Bryant, Penny; Bird, Matthew; Henseleit, Korinna; Swierkosz, Julia; Parekh, Vimal; Tommasi, Rita; Pawlisz, Estera; Jurlewicz, Kosma; Farys, Monika; Camper, Nicolas; Sheng, XiaoBo; Fisher, Martin; Grygorash, Ruslan; Kyle, Andrew; Abhilash, Amrita; Frigerio, Mark; Edwards, Jeff; Godwin, Antony
  Bioconjugate Chemistry (2014), 25 (6), 1124-1136CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
  To improve both the homogeneity and the stability of ADCs, we have developed site-specific drug-conjugating reagents that covalently rebridge reduced disulfide bonds. The new reagents comprise a drug, a linker, and a bis-reactive conjugating moiety that is capable of undergoing reaction with both sulfur atoms derived from a reduced disulfide bond in antibodies and antibody fragments. A disulfide rebridging reagent comprising monomethyl auristatin E (MMAE) was prepd. and conjugated to trastuzumab (TRA). A 78% conversion of antibody to ADC with a drug to antibody ratio (DAR) of 4 was achieved with no unconjugated antibody remaining. The MMAE rebridging reagent was also conjugated to the interchain disulfide of a Fab derived from proteolytic digestion of TRA, to give a homogeneous single drug conjugated product. The resulting conjugates retained antigen-binding, were stable in serum, and demonstrated potent and antigen-selective cell killing in in vitro and in vivo cancer models. Disulfide rebridging conjugation is a general approach to prep. stable ADCs, which does not require the antibody to be recombinantly re-engineered for site-specific conjugation.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXntlGisr4%253D&md5=24c6fcdb6aafa32b28f3b269e04f580c
  (b) Wang, T.; Ng, D. Y. W.; Wu, Y.; Thomas, J.; TamTran, T.; Weil, T. Chem. Commun. 2014, 50, 1116
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  93b
  Bis-sulfide bioconjugates for glutathione triggered tumor responsive drug release
  Wang, Tao; Ng, David Y. W.; Wu, Yuzhou; Thomas, Jessica; TamTran, Thuy; Weil, Tanja
  Chemical Communications (Cambridge, United Kingdom) (2014), 50 (9), 1116-1118CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
  The reaction of bis-sulfone conjugation reagents with disulfide bonds allows the site-specific modification of various peptides and proteins. Herein, we present the intracellular disintegration of bis-sulfide contg. somatostatin bioconjugates under controlled, tumor-relevant glutathione levels. GSH responsive release is demonstrated, which offers high potential for designing tumor responsive therapeutics.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhvFyrt7bO&md5=4745ae77e2a6c6e915b5688a85e5eb12
  (c) Wang, T.; Wu, Y.; Kuan, S. L.; Dumele, O.; Lamla, M.; Ng, D. Y. W.; Arzt, M.; Thomas, J.; Mueller, J. O.; Barner-Kowollik, C.; Weil, T. Chem.—Eur. J. 2015, 21, 228
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  93c
  A Disulfide Intercalator Toolbox for the Site-Directed Modification of Polypeptides
  Wang, Tao; Wu, Yuzhou; Kuan, Seah Ling; Dumele, Oliver; Lamla, Markus; Ng, David Y. W.; Arzt, Matthias; Thomas, Jessica; Mueller, Jan O.; Barner-Kowollik, Christopher; Weil, Tanja
  Chemistry - A European Journal (2015), 21 (1), 228-238CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)
  A disulfide intercalator toolbox was developed for site-specific attachment of a broad variety of functional groups to proteins or peptides under mild, physiol. conditions. The peptide hormone somatostatin (SST) served as model compd. for intercalation into the available disulfide functionalization schemes starting from the intercalator or the reactive SST precursor before or after bioconjugation. A tetrazole-SST deriv. was obtained that undergoes photoinduced cycloaddn. in mammalian cells, which was monitored by live-cell imaging.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXitFamsLjN&md5=d0e7ecbf8da12acdaeaf23c412121045
94. 94
  Cong, Y.; Pawlisz, E.; Bryant, P.; Balan, S.; Laurine, E.; Tommasi, R.; Singh, R.; Dubey, S.; Peciak, K.; Bird, M.; Sivasankar, A.; Swierkosz, J.; Muroni, M.; Heidelberger, S.; Farys, M.; Khayrzad, F.; Edwards, J.; Badescu, G.; Hodgson, I.; Heise, C.; Somavarapu, S.; Liddell, J.; Powell, K.; Zloh, M.; Choi, J.-W.; Godwin, A.; Brocchini, S. Bioconjugate Chem. 2012, 23, 248
  [ ACS Full Text ], [ CAS], Google Scholar
  94
  Site-Specific PEGylation at Histidine Tags
  Cong, Yuehua; Pawlisz, Estera; Bryant, Penny; Balan, Sibu; Laurine, Emmanuelle; Tommasi, Rita; Singh, Ruchi; Dubey, Sitara; Peciak, Karolina; Bird, Matthew; Sivasankar, Amrita; Swierkosz, Julia; Muroni, Maurizio; Heidelberger, Sibylle; Farys, Monika; Khayrzad, Farzad; Edwards, Jeff; Badescu, George; Hodgson, Ian; Heise, Charles; Somavarapu, Satyanarayana; Liddell, John; Powell, Keith; Zloh, Mire; Choi, Ji-won; Godwin, Antony; Brocchini, Steve
  Bioconjugate Chemistry (2012), 23 (2), 248-263CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
  The efficacy of protein-based medicines can be compromised by their rapid clearance from the blood circulatory system. Achieving optimal pharmacokinetics is a key requirement for the successful development of safe protein-based medicines. Protein PEGylation is a clin. proven strategy to increase the circulation half-life of protein-based medicines. One limitation of PEGylation is that there are few strategies that achieve site-specific conjugation of PEG to the protein. Here, we describe the covalent conjugation of PEG site-specifically to a polyhistidine tag (His-tag) on a protein. His-tag site-specific PEGylation was achieved with a domain antibody (dAb) that had a 6-histidine His-tag on the C-terminus (dAb-His6) and interferon α-2a (IFN) that had an 8-histidine His-tag on the N-terminus (His8-IFN). The site of PEGylation at the His-tag for both dAb-His6-PEG and PEG-His8-IFN was confirmed by digestion, chromatog., and mass-spectral studies. A methionine was also inserted directly after the N-terminal His-tag in IFN to give His8Met-IFN. Cyanogen bromide digestion studies of PEG-His8Met-IFN were also consistent with PEGylation at the His-tag. By using increased stoichiometries of the PEGylation reagent, it was possible to conjugate two sep. PEG mols. to the His-tag of both the dAb and IFN proteins. Stability studies followed by in vitro evaluation confirmed that these PEGylated proteins retained their biol. activity. In vivo PK studies showed that all of the His-tag PEGylated samples displayed extended circulation half-lives. Together, our results indicate that site-specific, covalent PEG conjugation at a His-tag can be achieved and biol. activity maintained with therapeutically relevant proteins.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xntlanuw%253D%253D&md5=fbd2c318cfd7a5c0c91384d229044e1d
95. 95
  (a) Bryden, F.; Maruani, A.; Savoie, H.; Chudasama, V.; Smith, M. E. B.; Caddick, S.; Boyle, R. W. Bioconjugate Chem. 2014, 25, 611
  [ ACS Full Text ], [ CAS], Google Scholar
  95a
  Regioselective and Stoichiometrically Controlled Conjugation of Photodynamic Sensitizers to a HER2 Targeting Antibody Fragment
  Bryden, Francesca; Maruani, Antoine; Savoie, Huguette; Chudasama, Vijay; Smith, Mark E. B.; Caddick, Stephen; Boyle, Ross W.
  Bioconjugate Chemistry (2014), 25 (3), 611-617CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
  The rapidly increasing interest in the synthesis of antibody-drug conjugates as powerful targeted anticancer agents demonstrates the growing appreciation of the power of antibodies and antibody fragments as highly selective targeting moieties. This targeting ability is of particular interest in the area of photodynamic therapy, as the applicability of current clin. photosensitizers is limited by their relatively poor accumulation in target tissue in comparison to healthy tissue. Although synthesis of porphyrin-antibody conjugates has been previously demonstrated, existing work in this area has been hindered by the limitations of conventional antibody conjugation methods. This work describes the attachment of azide-functionalized, water-sol. porphyrins to a trastuzumab Fab fragment via a novel conjugation methodol. This method allows for the synthesis of a homogeneous product without the loss of structural stability assocd. with conventional methods of disulfide modification. Biol. evaluation of the synthesized conjugates demonstrates excellent selectivity for a HER2 pos. cell line over the control, with no dark toxicity obsd. in either case.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXivFOgsb4%253D&md5=d7ba37c879f3c6b087012d724fa784f1
  (b) Jones, M. W.; Strickland, R. A.; Schumacher, F. F.; Caddick, S.; Baker, J. R.; Gibson, M. I.; Haddleton, D. M. J. Am. Chem. Soc. 2012, 134, 1847
  [ ACS Full Text ], [ CAS], Google Scholar
  95b
  Polymeric Dibromomaleimides As Extremely Efficient Disulfide Bridging Bioconjugation and Pegylation Agents
  Jones, Mathew W.; Strickland, Rachel A.; Schumacher, Felix F.; Caddick, Stephen; Baker, James. R.; Gibson, Matthew I.; Haddleton, David M.
  Journal of the American Chemical Society (2012), 134 (3), 1847-1852CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  A series of dibromomaleimides are very efficacious at insertion into peptidic disulfide bonds. This conjugation proceeds with a stoichiometric balance of reagents in buffered solns. in <15 min to give discrete products while maintaining the disulfide bridge and thus peptide conformation. The insertion is initiated by disulfide redn. using a water-sol. phosphine, tris(2-carboxyethyl)phosphine (TCEP) which allows for subsequent substitution of the two maleimide bromides by the generated thiols. Reaction of salmon calcitonin (sCT) with 2,3-dibromomaleimide (1.1 excess) in the presence of TCEP (1.1 equiv) in aq. soln. at pH 6.2 gives complete prodn. of a single conjugate which requires no workup. A linear methoxy poly(ethylene glycol) (PEG) was functionalized via a Mitsunobu reaction and used for the successful site-specific and rapid pegylation of sCT. This reaction occurs in 15 min with a small stoichiometry excess of the pegylating agent to give insertion at the disulfide with HPLC showing a single product and MALDI-ToF confirming conjugation. Attempts to use the group in a functional ATRP polymn. initiator led to polymn. inhibition. Thus, to prep. a range of functional polymers, an indirect route was chosen via both azide and aniline functional initiators which were converted to 2,3-dibromomaleimides via appropriate reactions. For example, the azide functional polymer was reacted via a Huisgen CuAAC click reaction to an alkyne functional 2,3-dibromomaleimide. This new reagent allowed for the synthesis of conjugates of sCT with comb polymers derived from PEG methacrylic monomers which in addn. gave appropriate cloud points. This reaction represents a highly efficient polymer conjugation method which circumvents problems of purifn. which normally arise from having to use large excesses of the conjugate. In addn., the tertiary structure of the peptide is efficiently maintained.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhs1CrsLnI&md5=d25a6e0952cbd96ed1a013c1057873b1
96. 96
  (a) Jones, M. W.; Strickland, R. A.; Schumacher, F. F.; Caddick, S.; Baker, J. R.; Gibson, M. I.; Haddleton, D. M. Chem. Commun. 2012, 48, 4064
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  96a
  Highly efficient disulfide bridging polymers for bioconjugates from radical-compatible dithiophenol maleimides
  Jones, Mathew W.; Strickland, Rachel A.; Schumacher, Felix F.; Caddick, Stephen; Baker, James. R.; Gibson, Matthew I.; Haddleton, David M.
  Chemical Communications (Cambridge, United Kingdom) (2012), 48 (34), 4064-4066CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
  The direct synthesis of dithiophenol maleimide functional polymers by living radical polymn. is described without the need for protecting group chem. The synthesized polymers have been successfully employed as disulfide bridging agents for salmon calcitonin when used in equimolar quantities, negating the requirement for complex purifn. strategies, traditionally assocd. with peptide bioconjugation.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xks1Olsrs%253D&md5=3676280121fa2cffb286523d982cc227
  (b) Schumacher, F. F.; Nunes, J. P. M.; Maruani, A.; Chudasama, V.; Smith, M. E. B.; Chester, K. A.; Baker, J. R.; Caddick, S. Org. Biomol. Chem. 2014, 12, 7261
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  96b
  Next generation maleimides enable the controlled assembly of antibody-drug conjugates via native disulfide bond bridging
  Schumacher, Felix F.; Nunes, Joao P. M.; Maruani, Antoine; Chudasama, Vijay; Smith, Mark E. B.; Chester, Kerry A.; Baker, James R.; Caddick, Stephen
  Organic & Biomolecular Chemistry (2014), 12 (37), 7261-7269CODEN: OBCRAK; ISSN:1477-0520. (Royal Society of Chemistry)
  The advent of Adcetris and Kadcyla, two recently FDA-approved antibody-drug conjugates (ADCs), in the clinic has had a major impact on the treatment of lymphoma and breast cancer patients, resp., worldwide. Despite these successes many new ADCs fail at various stages of development, often due to shortcomings in the methods used for their assembly. To address this problem we have developed next generation maleimides (NGMs), which specifically re-bridge reduced interchain disulfide bonds and allow the efficient conjugation of small mols. to antibodies, without the need for engineering of the target antibody. The method is site-specific and generates near homogeneous products in good yields. Moreover, adjustment of the reaction conditions allows control of the conjugation in terms of stoichiometry (drug-loading) and site selectivity. Using this method we prepd. a series of ADCs from trastuzumab and doxorubicin (DOX) with a controlled drug-to-antibody ratio (DAR) of 1, 2, 3 and 4. All of these constructs were fully active by ELISA and had more than 90% of re-bridged disulfide bonds by CE-SDS when compared to clin. grade antibody. Furthermore, digest expts. of the DAR 2 material revealed that almost all of the drug had been targeted to the Fab arms of the antibody. Thus, NGMs offer a flexible and simple platform for the controlled assembly of ADCs from an antibody.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtlahtrjL&md5=7789c927968a1ea63d48cac5f5fd5836
97. 97
  Castañeda, L.; Maruani, A.; Schumacher, F. F.; Miranda, E.; Chudasama, V.; Chester, K. A.; Baker, J. R.; Smith, M. E. B.; Caddick, S. Chem. Commun. 2013, 49, 8187
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  97
  Acid-cleavable thiomaleamic acid linker for homogeneous antibody-drug conjugation
  Castaneda, Lourdes; Maruani, Antoine; Schumacher, Felix F.; Miranda, Enrique; Chudasama, Vijay; Chester, Kerry A.; Baker, James R.; Smith, Mark E. B.; Caddick, Stephen
  Chemical Communications (Cambridge, United Kingdom) (2013), 49 (74), 8187-8189CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
  In this communication we describe a novel acid-cleavable linker strategy for antibody-drug conjugation. Functional disulfide bridging of the single interchain disulfide bond of a trastuzumab Fab fragment yields a homogeneous antibody-drug conjugate bearing a thiomaleamic acid linker. This linker is stable at physiol. pH and temp., but quant. cleaves at lysosomal pH to release the drug payload.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtlWjsrvM&md5=63dbcd8a78a7bdbb599ff1e742cb35f5
98. 98
  Hull, E. A.; Livanos, M.; Miranda, E.; Smith, M. E. B.; Chester, K. A.; Baker, J. R. Bioconjugate Chem. 2014, 25, 1395
  [ ACS Full Text ], [ CAS], Google Scholar
  98
  Homogeneous Bispecifics by Disulfide Bridging
  Hull, Elizabeth A.; Livanos, Maria; Miranda, Enrique; Smith, Mark E. B.; Chester, Kerry A.; Baker, James R.
  Bioconjugate Chemistry (2014), 25 (8), 1395-1401CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
  We report on a chem. platform to generate site-specific, homogeneous, antibody-antibody conjugates by targeting and bridging disulfide bonds. A bispecific antibody construct was produced in good yield through simple redn. and bridging of antibody fragment disulfide bonds, using a readily synthesized bis-dibromomaleimide cross-linker. Binding activity of antibodies was maintained, and in vitro binding of target antigens was obsd. This technol. is demonstrated through linking scFv and Fab antibody fragments, showing its potential for the construction of a diverse range of bispecifics.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtFOhu7%252FK&md5=764f9e1917af2387525b5244cedc6a2d
99. 99
  (a) Dhal, P. K.; Polomoscanik, S. C.; Gianolio, D. A.; Starremans, P. G.; Busch, M.; Alving, K.; Chen, B.; Miller, R. J. Bioconjugate Chem. 2013, 24, 865
  [ ACS Full Text ], [ CAS], Google Scholar
  99a
  Well-Defined Aminooxy Terminated N-(2-Hydroxypropyl) Methacrylamide Macromers for Site Specific Bioconjugation of Glycoproteins
  Dhal, Pradeep K.; Polomoscanik, Steven C.; Gianolio, Diego A.; Starremans, Patrick G.; Busch, Michelle; Alving, Kim; Chen, Bo; Miller, Robert J.
  Bioconjugate Chemistry (2013), 24 (6), 865-877CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
  Syntheses and characterization of aminooxy terminated polymers of N-(2-hydroxypropyl) methacrylamide (HPMA) of controlled mol. wt. and narrow mol. wt. distribution are presented here. Design of a chain transfer agent (CTA) contg. N-tert-butoxycarbonyl (t-Boc) protected aminooxy group enabled us to use reversible addn.-fragmentation (RAFT) polymn. technique to polymerize the HPMA monomer. An amide bond was utilized to link the aminooxy group and the CTA through a triethylene glycol spacer. As a result, the aminooxy group is linked to the poly(HPMA) backbone through a hydrolytically stable amide bond. By varying the monomer to initiator ratios, polymers with targeted mol. wts. were obtained. The mol. wts. of the polymers were detd. by gel permeation chromatog. (GPC) and mass spectrometry (ESI and MALDI-TOF). The t-Boc protecting group was quant. removed to generate aminooxy terminated poly(HPMA) macromers. These macromers were converted to rhodamine B terminated poly(HPMA) by reacting N-hydroxysuccinimide (NHS) ester of the dye with the terminal aminooxy group to form a stable alkoxyamide bond. Utility of these dye-labeled polymers as mol. probes was evaluated by fluorescence microscopy by studying their intracellular uptake by renal epithelial cells. These aminooxy terminated poly(HPMA) were also tested as biocompatible carriers to prep. chemoselective bioconjugates of proteins using transferrin (Tf) as the protein. Oxidn. of the sialic acid side chains of Tf generated aldehyde functionalized protein that was reacted with aminooxy terminated poly(HPMA), which resulted in protein-polymer bioconjugates carrying oxime linkages. These bioconjugates were characterized by gel electrophoresis and MALDI-TOF mass spectrometry.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXmslSnu7Y%253D&md5=42b0571835fdf858f873263d03925573
  (b) Zuberbühler, K.; Casi, G.; Bernardes, G. J. L.; Neri, D. Chem. Commun. 2012, 48, 7100
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  99b
  Fucose-specific conjugation of hydrazide derivatives to a vascular-targeting monoclonal antibody in IgG format
  Zuberbuhler Kathrin; Casi Giulio; Bernardes Goncalo J L; Neri Dario
  Chemical communications (Cambridge, England) (2012), 48 (56), 7100-2 ISSN:.
  We describe a method that enables specific and efficient conjugation of hydrazide-moieties to an IgG targeting the tumor neovasculature. The resulting chemically defined, homogeneous hydrazone-linked IgG conjugates remain immunoreactive and have a half-life of approximately 18 hours at physiological pH and temperature suitable for localized delivery of toxic drugs.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC38jgsVCksQ%253D%253D&md5=0c3adabc3e3312c3c32d149c7a2adcdf
  (c) Zeng, Y.; Ramya, T. N. C.; Dirksen, A.; Dawson, P. E.; Paulson, J. C. Nat. Methods 2009, 6, 207
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  99c
  High-efficiency labeling of sialylated glycoproteins on living cells
  Zeng, Ying; Ramya, T. N. C.; Dirksen, Anouk; Dawson, Philip E.; Paulson, James C.
  Nature Methods (2009), 6 (3), 207-209CODEN: NMAEA3; ISSN:1548-7091. (Nature Publishing Group)
  The authors describe a simple method for efficiently labeling cell-surface sialic acid-contg. glycans on living animal cells. The method uses mild periodate oxidn. to generate an aldehyde on sialic acids, followed by aniline-catalyzed oxime ligation with a suitable tag. Aniline catalysis dramatically accelerates oxime ligation, allowing use of low concns. of aminooxy-biotin at neutral pH to label the majority of cell-surface sialylated glycoproteins while maintaining high cell viability.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXitFKltbw%253D&md5=810924d8945721f21b91b2f757a7fc06
  (d) Zhang, H.; Li, X.-j.; Martin, D. B.; Aebersold, R. Nat. Biotechnol. 2003, 21, 660
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  99d
  Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry
  Zhang, Hui; Li, Xiao-jun; Martin, Daniel B.; Aebersold, Ruedi
  Nature Biotechnology (2003), 21 (6), 660-666CODEN: NABIF9; ISSN:1087-0156. (Nature Publishing Group)
  Quant. proteome profiling using stable isotope protein tagging and automated tandem mass spectrometry (MS/MS) is an emerging technol. with great potential for the functional anal. of biol. systems and for the detection of clin. diagnostic or prognostic marker proteins. Owing to the enormous complexity of proteomes, their comprehensive anal. is an as-yet-unresolved tech. challenge. However, biol. or clin. important information can be obtained if specific, information-rich protein classes, or sub-proteomes, are isolated and analyzed. Glycosylation is the most common post-translational modification. Here we describe a method for the selective isolation, identification and quantification of peptides that contain N-linked carbohydrates. It is based on the conjugation of glycoproteins to a solid support using hydrazide chem., stable isotope labeling of glycopeptides and the specific release of formerly N-linked glycosylated peptides via peptide- N-glycosidase F (PNGase F). The recovered peptides are then identified and quantified by MS/MS. We applied the approach to the anal. of plasma membrane proteins and proteins contained in human blood serum.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXktFSlu7s%253D&md5=9374aa7ce1950b38ce7d1b11aaf2e0d5
100. 100
  Witus, L. S.; Netirojjanakul, C.; Palla, K. S.; Muehl, E. M.; Weng, C.-H.; Iavarone, A. T.; Francis, M. B. J. Am. Chem. Soc. 2013, 135, 17223
  [ ACS Full Text ], [ CAS], Google Scholar
  100
  Site-Specific Protein Transamination Using N-Methylpyridinium-4-carboxaldehyde
  Witus, Leah S.; Netirojjanakul, Chawita; Palla, Kanwal S.; Muehl, Ellen M.; Weng, Chih-Hisang; Iavarone, Anthony T.; Francis, Matthew B.
  Journal of the American Chemical Society (2013), 135 (45), 17223-17229CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  The controlled attachment of synthetic groups to proteins is important for a no. of fields, including therapeutics, where antibody-drug conjugates are an emerging area of biol. medicines. We have previously reported a site-specific protein modification method using a transamination reaction that chemoselectively oxidizes the N-terminal amine of a polypeptide chain to a ketone or an aldehyde group. The newly introduced carbonyl can be used for conjugation to a synthetic group in one location through the formation of an oxime or a hydrazone linkage. To expand the scope of this reaction, we have used a combinatorial peptide library screening platform as a method to explore new transamination reagents while simultaneously identifying their optimal N-terminal sequences. N-Methylpyridinium-4-carboxaldehyde benzenesulfonate salt (Rapoport's salt, RS) was identified as a highly effective transamination reagent when paired with glutamate-terminal peptides and proteins. This finding establishes RS as a transamination reagent that is particularly well suited for antibody modification. Using a known therapeutic antibody, herceptin, it was demonstrated that RS can be used to modify the heavy chains of the wild-type antibody or to modify both the heavy and the light chains after N-terminal sequence mutation to add addnl. glutamate residues.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhslaksLfP&md5=d75726e44873a838e49c4efd50142a79
101. 101
  Carrico, I. S.; Carlson, B. L.; Bertozzi, C. R. Nat. Chem. Biol. 2007, 3, 321
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  101
  Introducing genetically encoded aldehydes into proteins
  Carrico, Isaac S.; Carlson, Brian L.; Bertozzi, Carolyn R.
  Nature Chemical Biology (2007), 3 (6), 321-322CODEN: NCBABT; ISSN:1552-4450. (Nature Publishing Group)
  Methods for introducing bioorthogonal functionalities into proteins have become central to protein engineering efforts. Here the authors describe a method for the site-specific introduction of aldehyde groups into recombinant proteins using the 6-amino-acid consensus sequence recognized by the formylglycine-generating enzyme. This genetically encoded 'aldehyde tag' is no larger than a His6 tag and can be exploited for numerous protein labeling applications.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXltlOjuro%253D&md5=a4a6643365248f08987086bfaa70f589
102. 102
  El-Mahdi, O.; Melnyk, O. Bioconjugate Chem. 2013, 24, 735
  [ ACS Full Text ], [ CAS], Google Scholar
  102
  α-Oxo Aldehyde or Glyoxylyl Group Chemistry in Peptide Bioconjugation
  El-Mahdi, Ouafaa; Melnyk, Oleg
  Bioconjugate Chemistry (2013), 24 (5), 735-765CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
  A review. Since the 1990s, α-oxo aldehyde or glyoxylic acid chem. has inspired a vast array of synthetic tools for tailoring peptide or protein structures, for developing peptides endowed with novel physicochem. properties or biol. functions, for assembling a large diversity of bioconjugates or hybrid materials, or for designing peptide-based micro or nanosystems. This past decade, important developments have enriched the α-oxo aldehyde synthetic tool box in peptide bioconjugation chem. and explored novel applications. The aim of this review is to give a large overview of this creative field.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXls1eitL0%253D&md5=1bf0d72d592062cb749749fe0d4d0473
103. 103
  (a) Smith, E. L.; Giddens, J. P.; Iavarone, A. T.; Godula, K.; Wang, L.-X.; Bertozzi, C. R. Bioconjugate Chem. 2014, 25, 788
  [ ACS Full Text ], [ CAS], Google Scholar
  103a
  Chemoenzymatic Fc Glycosylation via Engineered Aldehyde Tags
  Smith, Elizabeth L.; Giddens, John P.; Iavarone, Anthony T.; Godula, Kamil; Wang, Lai-Xi; Bertozzi, Carolyn R.
  Bioconjugate Chemistry (2014), 25 (4), 788-795CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
  Glycoproteins with chem. defined glycosylation sites and structures are important biopharmaceutical targets and crit. tools for glycobiol. One approach toward constructing such mols. involves chem. glycosylation of aldehyde-tagged proteins. Here, we report the installation of a genetically encoded aldehyde tag at the internal glycosylation site of the crystallizable fragment (Fc) of IgG1. We replaced the natural Fc N-glycosylation sequon with a five amino-acid sequence that was efficiently converted by recombinant formylglycine generating enzyme in vitro, thereby introducing aldehyde groups for subsequent chem. elaboration. Oxime-linked glycoconjugates were synthesized by conjugating aminooxy N-acetylglucosamine to the modified Fc followed by enzymic transfer of complex N-glycans from corresponding glycan oxazolines by an EndoS-derived glycosynthase. In this manner we generated specific Fc glycoforms without relying on natural protein glycosylation machineries.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXktl2hsr8%253D&md5=4550a9f372542a49c48ab0260e1faef8
  (b) Hudak, J. E.; Barfield, R. M.; de Hart, G. W.; Grob, P.; Nogales, E.; Bertozzi, C. R.; Rabuka, D. Angew. Chem., Int. Ed. 2012, 51, 4161
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  103b
  Synthesis of heterobifunctional protein fusions using copper-free click chemistry and the aldehyde tag
  Hudak, Jason E.; Barfield, Robyn M.; de Hart, Gregory W.; Grob, Patricia; Nogales, Eva; Bertozzi, Carolyn R.; Rabuka, David
  Angewandte Chemie, International Edition (2012), 51 (17), 4161-4165, S4161/1-S4161/16CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
  Cu-free click chem. in conjunction with the aldehyde tag can produce protein-protein chem. conjugates of unprecedented size and complexity. The synthetic route capitalizes on small-mol. linkers that can increase reaction yields, lower the necessary reagent concns., and decrease the reaction time. The method should expand the topologies of available protein fusions and allow the exploration of alternate points of protein-protein attachment.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XjsFCqt74%253D&md5=b081b97d56b0eac40a3e2c81c61f1f56
  (c) Ng, S.; Jafari, M. R.; Matochko, W. L.; Derda, R. ACS Chem. Biol. 2012, 7, 1482
  [ ACS Full Text ], [ CAS], Google Scholar
  103c
  Quantitative Synthesis of Genetically Encoded Glycopeptide Libraries Displayed on M13 Phage
  Ng, Simon; Jafari, Mohammad R.; Matochko, Wadim L.; Derda, Ratmir
  ACS Chemical Biology (2012), 7 (9), 1482-1487CODEN: ACBCCT; ISSN:1554-8929. (American Chemical Society)
  Phage display is a powerful technol. that enables the discovery of peptide ligands for many targets. Chem. modification of phage libraries have allowed the identification of ligands with properties not encountered in natural polypeptides. In this report, we demonstrated the synthesis of 2 × 108 genetically encoded glycopeptides from a com. available phage-displayed peptide library (Ph.D.-7) in a two-step, one-pot reaction in <1.5 h. Unlike previous reports, we bypassed genetic engineering of phage. The glycan moiety was introduced via an oxime ligation following oxidn. of an N-terminal Ser/Thr; these residues are present in the peptide libraries at 20-30% abundance. The construction of libraries was facilitated by simple characterization, which directly assessed the yield and regioselectivity of chem. reactions performed on phage. This quantification method also allowed facile yield detn. of reactions in 109 distinct mols. We envision that the methodol. described herein will find broad application in the synthesis of custom chem. modified phage libraries.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XptVWmsrc%253D&md5=012c744473e9f076da1f7df02e490b5c
  (d) Kularatne, S. A.; Deshmukh, V.; Ma, J.; Tardif, V.; Lim, R. K. V.; Pugh, H. M.; Sun, Y.; Manibusan, A.; Sellers, A. J.; Barnett, R. S.; Srinagesh, S.; Forsyth, J. S.; Hassenpflug, W.; Tian, F.; Javahishvili, T.; Felding-Habermann, B.; Lawson, B. R.; Kazane, S. A.; Schultz, P. G. Angew. Chem., Int. Ed. 2014, 53, 11863
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  103d
  A CXCR4-Targeted Site-Specific Antibody-Drug Conjugate
  Kularatne, Sumith A.; Deshmukh, Vishal; Ma, Jennifer; Tardif, Virginie; Lim, Reyna K. V.; Pugh, Holly M.; Sun, Ying; Manibusan, Anthony; Sellers, Aaron J.; Barnett, Richard S.; Srinagesh, Shailaja; Forsyth, Jane S.; Hassenpflug, Wolf; Tian, Feng; Javahishvili, Tsotne; Felding-Habermann, Brunhilde; Lawson, Brian R.; Kazane, Stephanie A.; Schultz, Peter G.
  Angewandte Chemie, International Edition (2014), 53 (44), 11863-11867CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
  A chem. defined anti-CXCR4-auristatin antibody-drug conjugate (ADC) was synthesized that selectively eliminates tumor cells overexpressing the CXCR4 receptor. The unnatural amino acid p-acetylphenylalanine (pAcF) was site-specifically incorporated into an anti-CXCR4 IgG and conjugated to an auristatin through a stable, noncleavable oxime linkage to afford a chem. homogeneous ADC. The full-length anti-CXCR4 ADC was selectively cytotoxic to CXCR4+ cancer cells in vitro (half maximal effective concn. (EC50)≈80-100 pM). Moreover, the anti-CXCR4 ADC eliminated pulmonary lesions from human osteosarcoma cells in a lung-seeding tumor model in mice. No significant overt toxicity was obsd. but there was a modest decrease in the bone-marrow-derived CXCR4+ cell population. Because CXCR4 is highly expressed in a majority of metastatic cancers, a CXCR4-auristatin ADC may be useful for the treatment of a variety of metastatic malignancies.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsFamu7rE&md5=30c4a48be95ebf4d797792281f4badf0
104. 104
  (a) Lu, Y.; Ngo Ndjock Mbong, G.; Liu, P.; Chan, C.; Cai, Z.; Weinrich, D.; Boyle, A. J.; Reilly, R. M.; Winnik, M. A. Biomacromolecules 2014, 15, 2027
  [ ACS Full Text ], [ CAS], Google Scholar
  104a
  Synthesis of Polyglutamide-Based Metal-Chelating Polymers and Their Site-Specific Conjugation to Trastuzumab for Auger Electron Radioimmunotherapy
  Lu, Yijie; Mbong, Ghislaine Ngo Ndjock; Liu, Peng; Chan, Conrad; Cai, Zhongli; Weinrich, Dirk; Reilly, Raymond M.; Winnik, Mitchell A.
  Biomacromolecules (2014), 15 (6), 2027-2037CODEN: BOMAF6; ISSN:1525-7797. (American Chemical Society)
  Three types of metal-chelating polymers (MCPs) with hydrazide end groups were synthesized. (1) The first set of polymers (the F-series) was synthesized with a furan end group, and all of the pendant groups along the chain carried only a diethylenetriaminepentaacetic acid (DTPA) metal-chelating functionality. The hydrazide was introduced via a Diels-Alder reaction between the furan and 3,3'-N-[ε-maleimidocaproic acid] hydrazide (EMCH). (2) The P-series polymers was designed to carry several copies of a nuclear-localization peptide sequence (NLS peptides, CGYGPKKKRKVGG, harboring the NLS from the simian virus 40 large T-antigen) in addn. to the DTPA metal-chelating groups. (3) The third type of polymer (the P-Py series) was a variation of the P-series polymers but with the introduction of a small no. of pyrene chromophores along the backbone to allow for UV measurement of the incorporation of the MCPs into trastuzumab (tmab). These hydrazide-terminated polymers were site-specifically conjugated to aldehyde groups generated by NaIO4 oxidn. of the pendant glycan in the Fc domain of tmab. The immunoconjugates were radiolabeled with 111In and analyzed by SE-HPLC to confirm the attachment of the polymer to the antibody. HER2 binding assays demonstrated that neither the MCPs nor the presence of the NLS peptides interfered with specific antigen recognition on SK-Br-3 cells, although nonspecific binding was increased by polymer conjugation. Our results suggest that MCPs can be site-specifically attached to antibodies via oxidized glycans in the Fc domain and labeled with 111In to construct radioimmunoconjugates with preserved immunoreactivity.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXotFCksLg%253D&md5=ab38eb6b3eefb6264cdff9ce54529ddc
  (b) Zhou, Z.; Zhang, J.; Sun, L.; Ma, G.; Su, Z. Bioconjugate Chem. 2013, 25, 138
  [ ACS Full Text ], Google Scholar
  There is no corresponding record for this reference.
105. 105
  Kitov, P. I.; Vinals, D. F.; Ng, S.; Tjhung, K. F.; Derda, R. J. Am. Chem. Soc. 2014, 136, 8149
  [ ACS Full Text ], [ CAS], Google Scholar
  105
  Rapid, Hydrolytically Stable Modification of Aldehyde-Terminated Proteins and Phage Libraries
  Kitov, Pavel I.; Vinals, Daniel F.; Ng, Simon; Tjhung, Katrina F.; Derda, Ratmir
  Journal of the American Chemical Society (2014), 136 (23), 8149-8152CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  The authors describe the rapid reaction of 2-amino benzamidoxime (ABAO) derivs. with aldehydes in water. The ABAO combines an aniline moiety for iminium-based activation of the aldehyde and a nucleophilic group (Nu:) ortho to the amine for intramol. ring closure. The reaction between ABAO and aldehydes is kinetically similar to oxime formations performed under stoichiometric aniline catalysis. The authors characterized the reaction by both NMR and UV spectroscopy and detd. that the rate-detg. step of the process is formation of a Schiff base, which is followed by rapid intramol. ring closure. The relation between apparent rate const. and pH suggests that a protonated benzamidoxime acts as an internal general acid in Schiff-base formation. The reaction is accelerated by substituents in the arom. ring that increase the basicity of the arom. amine. The rate of up to 40 M-1s-1 between an electron-rich aldehyde and 5-methoxy-ABAO (PMA), which was obsd. at pH 4.5, places this reaction among the fastest known bio-orthogonal reactions. Reaction between M13 phage-displayed library of peptides terminated with an aldehyde moiety and 1 mM biotin-ABAO deriv. reaches completion in 1 h at pH 4.5. Finally, the product of reaction, dihydroquinazoline deriv., shows fluorescence at 490 nm suggesting a possibility of developing fluorogenic aldehyde-reactive probes based on ABAO framework.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXosVOgu78%253D&md5=a63e11d567c40404430d58ba793f472a
106. 106
  Agarwal, P.; van der Weijden, J.; Sletten, E. M.; Rabuka, D.; Bertozzi, C. R. Proc. Natl. Acad. Sci. U. S. A. 2013, 110, 46
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  106
  A Pictet-Spengler ligation for protein chemical modification
  Agarwal Paresh; van der Weijden Joep; Sletten Ellen M; Rabuka David; Bertozzi Carolyn R
  Proceedings of the National Academy of Sciences of the United States of America (2013), 110 (1), 46-51 ISSN:.
  Aldehyde- and ketone-functionalized proteins are appealing substrates for the development of chemically modified biotherapeutics and protein-based materials. Their reactive carbonyl groups are typically conjugated with α-effect nucleophiles, such as substituted hydrazines and alkoxyamines, to generate hydrazones and oximes, respectively. However, the resulting C=N linkages are susceptible to hydrolysis under physiologically relevant conditions, which limits the utility of such conjugates in biological systems. Here we introduce a Pictet-Spengler ligation that is based on the classic Pictet-Spengler reaction of aldehydes and tryptamine nucleophiles. The ligation exploits the bioorthogonal reaction of aldehydes and alkoxyamines to form an intermediate oxyiminium ion; this intermediate undergoes intramolecular C-C bond formation with an indole nucleophile to form an oxacarboline product that is hydrolytically stable. We used the reaction for site-specific chemical modification of glyoxyl- and formylglycine-functionalized proteins, including an aldehyde-tagged variant of the therapeutic monoclonal antibody Herceptin. In conjunction with techniques for site-specific introduction of aldehydes into proteins, the Pictet-Spengler ligation offers a means to generate stable bioconjugates for medical and materials applications.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3s3hslKruw%253D%253D&md5=17780fe48052ef11b12ef85f357bfa2d
107. 107
  Agarwal, P.; Kudirka, R.; Albers, A. E.; Barfield, R. M.; de Hart, G. W.; Drake, P. M.; Jones, L. C.; Rabuka, D. Bioconjugate Chem. 2013, 24, 846
  [ ACS Full Text ], [ CAS], Google Scholar
  107
  Hydrazino-Pictet-Spengler Ligation as a Biocompatible Method for the Generation of Stable Protein Conjugates
  Agarwal, Paresh; Kudirka, Romas; Albers, Aaron E.; Barfield, Robyn M.; de Hart, Gregory W.; Drake, Penelope M.; Jones, Lesley C.; Rabuka, David
  Bioconjugate Chemistry (2013), 24 (6), 846-851CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
  Aldehyde- and ketone-functionalized biomols. have found widespread use in biochem. and biotechnol. fields. They are typically conjugated with hydrazide or aminooxy nucleophiles under acidic conditions to yield hydrazone or oxime products that are relatively stable, but susceptible to hydrolysis over time. The authors introduce a new reaction, the hydrazino-Pictet-Spengler (HIPS) ligation, which has two distinct advantages over hydrazone and oxime ligations. First, the HIPS ligation proceeds quickly near neutral pH, allowing for one-step labeling of aldehyde-functionalized proteins under mild conditions. Second, the HIPS ligation product is very stable (>5 days) in human plasma relative to an oxime-linked conjugate (∼1 day), as demonstrated by monitoring protein-fluorophore conjugates by ELISA. Thus, the HIPS ligation exhibits a combination of product stability and speed near neutral pH that is unparalleled by current carbonyl bioconjugation chemistries.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXot1GktLk%253D&md5=a65be6fe8a29a194aef2a9e97009f8cf
108. 108
  Drake, P. M.; Albers, A. E.; Baker, J.; Banas, S.; Barfield, R. M.; Bhat, A. S.; de Hart, G. W.; Garofalo, A. W.; Holder, P.; Jones, L. C.; Kudirka, R.; McFarland, J.; Zmolek, W.; Rabuka, D. Bioconjugate Chem. 2014, 25, 1331
  [ ACS Full Text ], [ CAS], Google Scholar
  108
  Aldehyde Tag Coupled with HIPS Chemistry Enables the Production of ADCs Conjugated Site-Specifically to Different Antibody Regions with Distinct in Vivo Efficacy and PK Outcomes
  Drake, Penelope M.; Albers, Aaron E.; Baker, Jeanne; Banas, Stefanie; Barfield, Robyn M.; Bhat, Abhijit S.; de Hart, Gregory W.; Garofalo, Albert W.; Holder, Patrick; Jones, Lesley C.; Kudirka, Romas; McFarland, Jesse; Zmolek, Wes; Rabuka, David
  Bioconjugate Chemistry (2014), 25 (7), 1331-1341CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
  It is becoming increasingly clear that site-specific conjugation offers significant advantages over conventional conjugation chemistries used to make antibody-drug conjugates (ADCs). Site-specific payload placement allows for control over both the drug-to-antibody ratio (DAR) and the conjugation site, both of which play an important role in governing the pharmacokinetics (PK), disposition, and efficacy of the ADC. In addn. to the DAR and site of conjugation, linker compn. also plays an important role in the properties of an ADC. The authors have previously reported a novel site-specific conjugation platform comprising linker payloads designed to selectively react with site-specifically engineered aldehyde tags on an antibody backbone. This chem. results in a stable C-C bond between the antibody and the cytotoxin payload, providing a uniquely stable connection with respect to the other linker chemistries used to generate ADCs. The flexibility and versatility of the aldehyde tag conjugation platform has enabled the authors to undertake a systematic evaluation of the impact of conjugation site and linker compn. on ADC properties. Here, the authors describe the prodn. and characterization of a panel of ADCs bearing the aldehyde tag at different locations on an IgG1 backbone conjugated using Hydrazino-iso-Pictet-Spengler (HIPS) chem. The authors demonstrate that in a panel of ADCs with aldehyde tags at different locations, the site of conjugation has a dramatic impact on in vivo efficacy and pharmacokinetic behavior in rodents; this advantage translates to an improved safety profile in rats as compared to a conventional lysine conjugate.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXps1Knurs%253D&md5=fb08b4277ea6d941861f1cca293b1385
109. 109
  Han, M.-J.; Xiong, D.-C.; Ye, X.-S. Chem. Commun. 2012, 48, 11079
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  109
  Enabling Wittig reaction on site-specific protein modification
  Han, Ming-Jie; Xiong, De-Cai; Ye, Xin-Shan
  Chemical Communications (Cambridge, United Kingdom) (2012), 48 (90), 11079-11081CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
  An efficient aq. Wittig reaction was enabled on protein bioconjugation for the first time. By investigating the reaction on small mols., peptides, and proteins, a site-specific reaction targeting "aldehyde tag" was presented. A variety of functional groups could be introduced into the protein of interest.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhsFCgt7bK&md5=965ac0249813eec7ec10eac47f37c8fd
110. 110
  Lum, K. M.; Xavier, V. J.; Ong, M. J. H.; Johannes, C. W.; Chan, K.-P. Chem. Commun. 2013, 49, 11188
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  110
  Stabilized Wittig olefination for bioconjugation
  Lum, Kenneth M.; Xavier, Vanessa J.; Ong, Michelle J.-H.; Johannes, Charles W.; Chan, Kok-Ping
  Chemical Communications (Cambridge, United Kingdom) (2013), 49 (95), 11188-11190CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
  Stabilized Wittig olefination holds great potential as a bioconjugation reaction. We demonstrate that the reaction of stabilized phosphorus ylides (or phosphonium salts) with aryl aldehydes is sufficiently robust to be used for live cell affinity isolation and fluorescence tagging of a protein, FKBP12.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhslWlsLnK&md5=bd16969717433cfb601d76a5775106b8
111. 111
  van Hest, J. C. M.; van Delft, F. L. ChemBioChem 2011, 12, 1309
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  111
  Protein Modification by Strain-Promoted Alkyne-Azide Cycloaddition
  van Hest, Jan C. M.; van Delft, Floris L.
  ChemBioChem (2011), 12 (9), 1309-1312CODEN: CBCHFX; ISSN:1439-4227. (Wiley-VCH Verlag GmbH & Co. KGaA)
  A review. Strain-promoted reactions between cyclooctynes and 1,3-dipoles have emerged as a versatile technol. for the modification of proteins. A broad range of methods has been developed for the introduction of azides (and other dipoles) into proteins, and a range of cyclooctynes has now become synthetically readily accessible or com. available. The emergence of these techniques will greatly expand the ability to prep. homogeneous protein conjugates (PEGylation, dimerization, spin-labeling, etc.) without the need for metals or reagents; this could be of great value for, for example, the manuf. of biopharmaceuticals. The recent demonstration that cyclooctyne can be genetically encoded into a protein will facilitate the direct read-out of protein tracking in living cells and potentially whole organisms, and is therefore a substantial extension of the bioconjugation toolbox. Cycloaddns. with other, more reactive dipoles than azide (e.g., nitrones or nitrile oxides) is also feasible now. Although the reactivity of cyclooctyn-3-ol is relatively low, the genetic encoding of more reactive cyclic alkynes is a logical next step.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXnt1Krsbw%253D&md5=118ebedf36f378517c3ee6a68a15cf27
112. 112
  (a) Ahad, A. M.; Jensen, S. M.; Jewett, J. C. Org. Lett. 2013, 15, 5060
  [ ACS Full Text ], [ CAS], Google Scholar
  112a
  A Traceless Staudinger Reagent To Deliver Diazirines
  Ahad, Ali M.; Jensen, Stephanie M.; Jewett, John C.
  Organic Letters (2013), 15 (19), 5060-5063CODEN: ORLEF7; ISSN:1523-7052. (American Chemical Society)
  A triarylphosphine reagent that reacts with org. azides to install amide-linked diazirines is reported [e.g., Staudinger-Bertozzi ligation of PhosDAz I with benzyl azide afforded diazirine amide II in 96% yield]. This traceless Staudinger reagent reacts with complex org. azides to yield amide-linked diazirines, thus expanding the scope of the utility of both azide and diazirine chem.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhsVyrtLnI&md5=7d2eec56727a5fc61edfb92ab2504f48
  (b) Bernardes, G. J. L.; Linderoth, L.; Doores, K. J.; Boutureira, O.; Davis, B. G. ChemBioChem 2011, 12, 1383
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  112b
  Site-Selective Traceless Staudinger Ligation for Glycoprotein Synthesis Reveals Scope and Limitations
  Bernardes, Goncalo J. L.; Linderoth, Lars; Doores, Katie J.; Boutureira, Omar; Davis, Benjamin G.
  ChemBioChem (2011), 12 (9), 1383-1386CODEN: CBCHFX; ISSN:1439-4227. (Wiley-VCH Verlag GmbH & Co. KGaA)
  The Staudinger reaction is another azide-selective reaction that has been used, for example, to modify cell surface carbohydrates, and to label proteins that contain an azidohomoalanine (Aha). Here, the authors prepd. a glucosyl phosphine deriv. and coupled it with an azide protein substrate using the traceless Staudinger reaction. The azide protein was fully consumed to give equimolar amts. of ligated amide product and reduced amine product.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXnt1Krsb4%253D&md5=a3bc19e896fa00a6d5218cee1607e063
113. 113
  Serwa, R.; Majkut, P.; Horstmann, B.; Swiecicki, J.-M.; Gerrits, M.; Krause, E.; Hackenberger, C. P. R. Chem. Sci. 2010, 596
  [ Crossref], [ CAS], Google Scholar
  113
  Site-specific PEGylation of proteins by a Staudinger-phosphite reaction
  Serwa, Remigiusz; Majkut, Paul; Horstmann, Benjamin; Swiecicki, Jean-Marie; Gerrits, Michael; Krause, Eberhard; Hackenberger, Christian P. R.
  Chemical Science (2010), 1 (5), 596-602CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)
  Current protocols in protein bioengineering allow the site-specific incorporation of chem. reporter moieties. Subsequently, these functional groups can be chemoselectively transformed to decorate proteins with charged and oversized functional units. Based on our recent report on the chemoselective reaction of azides with phosphites, we now apply the Staudinger-phosphite reaction to an efficient and metal-free PEGylation of an azide-contg. protein with sym. phosphites. Thereby, two types of branched oligoethylene glycol scaffolds are generated, which deliver either a stable or light-cleavable protein-PEG conjugate. Furthermore, we demonstrate that the Staudinger-phosphite reaction is an efficient transformation in both aq. media as well as in a highly crowded bacterial cell lysate.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXht1OgsbjE&md5=87116fe4116df6e153a271d9d0bf0c5b
114. 114
  Vallée, M. R. J.; Majkut, P.; Wilkening, I.; Weise, C.; Müller, G.; Hackenberger, C. P. R. Org. Lett. 2011, 13, 5440
  [ ACS Full Text ], [ CAS], Google Scholar
  114
  Staudinger-Phosphonite Reactions for the Chemoselective Transformation of Azido-Containing Peptides and Proteins
  Vallee, M. Robert J.; Majkut, Paul; Wilkening, Ina; Weise, Christoph; Mueller, Gregor; Hackenberger, Christian P. R.
  Organic Letters (2011), 13 (20), 5440-5443CODEN: ORLEF7; ISSN:1523-7052. (American Chemical Society)
  Site-specific functionalization of proteins by bioorthogonal modification offers a convenient pathway to create, modify, and study biol. active biopolymers. In this paper the Staudinger reaction of aryl-phosphonites for the chemoselective functionalization of azido-peptides and proteins was probed. Different water-sol. phosphonites with oligoethylene substituents were synthesized and reacted with unprotected azido-contg. peptides in aq. systems at room temp. in high conversions. Finally, the Staudinger-phosphonite reaction was successfully applied to the site-specific modification of the protein calmodulin.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXht1ClsbzO&md5=c79e0fee41ef9adfddd8bfdc0d7f22f9
115. 115
  Debets, M. F.; van Berkel, S. S.; Dommerholt, J.; Dirks, A. J.; Rutjes, F. P. J. T.; van Delft, F. L. Acc. Chem. Res. 2011, 44, 805
  [ ACS Full Text ], [ CAS], Google Scholar
  115
  Bioconjugation with Strained Alkenes and Alkynes
  Debets, Marjoke F.; van Berkel, Sander S.; Dommerholt, Jan; Dirks, A. J.; Rutjes, Floris P. J. T.; van Delft, Floris L.
  Accounts of Chemical Research (2011), 44 (9), 805-815CODEN: ACHRE4; ISSN:0001-4842. (American Chemical Society)
  A review. The structural complexity of mols. isolated from biol. sources has always served as an inspiration for org. chemists. Since the first synthesis of a natural product, urea, chemists have been challenged to prep. exact copies of natural structures in the lab. As a result, a broad repertoire of synthetic transformations has been developed over the years. It is now feasible to synthesize org. mols. of enormous complexity, and also mols. with less structural complexity but prodigious societal impact, such as nylon, TNT, polystyrene, statins, estradiol, XTC, and many more. Unfortunately, only a few chem. transformations are so mild and precise that they can be used to selectively modify biochem. structures, such as proteins or nucleic acids; these are the so-called bioconjugation strategies. Even more challenging is to apply a chem. reaction on or in living cells or whole organisms; these are the so-called bioorthogonal reactions. These fields of research are of particular importance because they not only pose a worthy challenge for chemists but also offer unprecedented possibilities for studying biol. systems, esp. in areas in which traditional biochem. and mol. biol. tools fall short. Recent years have seen tremendous growth in the chem. biol. toolbox. In particular, a rapidly increasing no. of bioorthogonal reactions has been developed based on chem. involving strained alkenes or strained alkynes. Such strained unsatd. systems have the unique ability to undergo (3+2) and (4+2) cycloaddns. with a diverse set of complementary reaction partners. Accordingly, chem. centered around strain-promoted cycloaddns. has been exploited to precisely modify biopolymers, ranging from nucleic acids to proteins to glycans. In this Account, the authors describe progress in bioconjugation centered around cycloaddns. of these strained unsatd. systems. Being among the first to recognize the utility of strain-promoted cycloaddns. between alkenes and dipoles, the authors highlight their report in 2007 of the reaction of oxanobornadienes with azides, which occurs through a sequential cycloaddn. and retro Diels-Alder reaction. The authors further consider the subsequent refinement of this reaction as a valuable tool in chem. biol. The authors also examine the development of the reaction of cyclooctyne, the smallest isolable cyclic alkyne, with a range of substrates. Owing to severe deformation of the triple bond from ideal linear geometry, the cyclooctynes show high reactivity toward dienes, 1,3-dipoles, and other mol. systems. In the search for bioorthogonal reactions, cycloaddns. of cyclic alkenes and alkynes have now established themselves as powerful tools in reagent-free bioconjugations.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXovFKmtbw%253D&md5=458aef02c8c2d806af82d04dfd4deb22
116. 116
  (a) Li, X.; Fang, T.; Boons, G.-J. Angew. Chem., Int. Ed. 2014, 53, 7179
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  116a
  Preparation of well-defined antibody-drug conjugates through glycan remodeling and strain-promoted azide-alkyne cycloadditions
  Li, Xiuru; Fang, Tao; Boons, Geert-Jan
  Angewandte Chemie, International Edition (2014), 53 (28), 7179-7182CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
  Antibody-drug conjugates hold considerable promise as anticancer agents, however, producing them remains a challenge and there is a need for mild, broadly applicable, site-specific conjugation methods that yield homogenous products. It was envisaged that enzymic remodeling of the oligosaccharides of an antibody would enable the introduction of reactive groups that can be exploited for the site-specific attachment of cytotoxic drugs. This is based on the observation that glycosyltransferases often tolerate chem. modifications in their sugar nucleotide substrates, thus allowing the installation of reactive functionalities. An azide was incorporated because this functional group is virtually absent in biol. systems and can be reacted by strain-promoted alkyne-azide cycloaddn. This method, which does not require genetic engineering, was used to produce an anti-CD22 antibody modified with doxorubicin to selectively target and kill lymphoma cells.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXos1aks7w%253D&md5=d59a17169fb0891a63e88960285c4f55
  (b) Zeglis, B. M.; Davis, C. B.; Aggeler, R.; Kang, H. C.; Chen, A.; Agnew, B. J.; Lewis, J. S. Bioconjugate Chem. 2013, 24, 1057
  [ ACS Full Text ], [ CAS], Google Scholar
  116b
  Enzyme-Mediated Methodology for the Site-Specific Radiolabeling of Antibodies Based on Catalyst-Free Click Chemistry
  Zeglis, Brian M.; Davis, Charles B.; Aggeler, Robert; Kang, Hee Chol; Chen, Aimei; Agnew, Brian J.; Lewis, Jason S.
  Bioconjugate Chemistry (2013), 24 (6), 1057-1067CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
  An enzyme- and click chem.-mediated methodol. for the site-selective radiolabeling of antibodies on the heavy chain glycans has been developed and validated. To this end, a model system based on the prostate specific membrane antigen-targeting antibody J591, the positron-emitting radiometal 89Zr, and the chelator desferrioxamine has been employed. The methodol. consists of four steps: (1) the removal of sugars on the heavy chain region of the antibody to expose terminal N-acetylglucosamine residues; (2) the incorporation of azide-modified N-acetylgalactosamine monosaccharides into the glycans of the antibody; (3) the catalyst-free click conjugation of desferrioxamine-modified dibenzocyclooctynes to the azide-bearing sugars; and (4) the radiolabeling of the chelator-modified antibody with 89Zr. The site-selective labeling methodol. proved facile, reproducible, and robust, producing 89Zr-labeled radioimmunoconjugates that display high stability and immunoreactivity in vitro (>95%) in addn. to highly selective tumor uptake (67.5 ± 5.0%ID/g) and tumor-to-background contrast in athymic nude mice bearing PSMA-expressing s.c. LNCaP xenografts. Ultimately, this strategy could play a crit. role in the development of novel well-defined and highly immunoreactive radioimmunoconjugates for both the lab. and clinic.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXnvVGjs70%253D&md5=ddea6ba4b4ce68903c6829cdc2ccd6c2
  (c) Zhou, Q.; Gui, J.; Pan, C.-M.; Albone, E.; Cheng, X.; Suh, E. M.; Grasso, L.; Ishihara, Y.; Baran, P. S. J. Am. Chem. Soc. 2013, 135, 12994
  [ ACS Full Text ], [ CAS], Google Scholar
  116c
  Bioconjugation by Native Chemical Tagging of C-H Bonds
  Zhou, Qianghui; Gui, Jinghan; Pan, Chung-Mao; Albone, Earl; Cheng, Xin; Suh, Edward M.; Grasso, Luigi; Ishihara, Yoshihiro; Baran, Phil S.
  Journal of the American Chemical Society (2013), 135 (35), 12994-12997CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  A general C-H functionalization method for the tagging of natural products and pharmaceuticals is described. An azide-contg. sulfinate reagent allows the appendage of azidoalkyl chains onto heteroaroms., the product of which can then be attached to a monoclonal antibody by a "click" reaction. This strategy expands the breadth of bioactive small mols. that can be linked to macromols. in a manner that is beyond the scope of existing methods in bioconjugation to permit tagging of the "seemingly untaggable".
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtlSjur3P&md5=dca0179112d7d412fa38073c986a0730
117. 117
  Jang, S.; Sachin, K.; Lee, H.-j.; Kim, D. W.; Lee, H. S. Bioconjugate Chem. 2012, 23, 2256
  [ ACS Full Text ], [ CAS], Google Scholar
  117
  Development of a Simple Method for Protein Conjugation by Copper-Free Click Reaction and Its Application to Antibody-Free Western Blot Analysis
  Jang, Sohye; Sachin, Kalme; Lee, Hui-jeong; Kim, Dong Wook; Lee, Hyun Soo
  Bioconjugate Chemistry (2012), 23 (11), 2256-2261CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
  There are currently many methods available for labeling proteins to study their structure and function. However, the utility of these methods is hampered by low efficiency, slow reaction rates, nonbiocompatible reaction conditions, large-sized labeling groups, and the requirement of specific side chains such as cysteine or lysine. A simple and efficient method for protein labeling was developed, in which an azide-contg. amino acid was introduced into a protein and conjugated to a labeling reagent by strain-promoted azide-alkyne cycloaddn. (SPAAC). This method allowed the authors to label proteins by simply mixing a protein and a labeling reagent in physiol. conditions with a labeling yield of ∼80% in 120 min. In addn., the specificity of SPAAC made it possible to analyze the expression level of a protein quant. by simple mixing and SDS-PAGE anal. with no need for antibodies or multistep incubations. Because the genetic incorporation of the azide-contg. amino acid can be generally applied to any protein and the SPAAC reaction is highly specific, this method should prove useful for labeling and analyzing proteins.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhsVGisrnP&md5=df6852fab28fdf6dbed759991560b4c4
118. 118
  van Geel, R.; Pruijn, G. J. M.; van Delft, F. L.; Boelens, W. C. Bioconjugate Chem. 2012, 23, 392
  [ ACS Full Text ], [ CAS], Google Scholar
  118
  Preventing Thiol-Yne Addition Improves the Specificity of Strain-Promoted Azide-Alkyne Cycloaddition
  van Geel, Remon; Pruijn, Ger J. M.; van Delft, Floris L.; Boelens, Wilbert C.
  Bioconjugate Chemistry (2012), 23 (3), 392-398CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
  The 1,3-dipolar cycloaddn. of azides with ring-strained alkynes is one of the few bioorthogonal reactions suitable for specific biomol. labeling in complex biol. systems. Nevertheless, azide-independent labeling of proteins by strained alkynes can occur to a varying extent, thereby limiting the sensitivity of assays based on strain-promoted azide-alkyne cycloaddn. (SPAAC). A subset of three cyclooctynes, dibenzocyclooctyne (DIBO), azadibenzocyclooctyne (DIBAC), and bicyclo[6.1.0]nonyne (BCN), was used to evaluate the azide-independent labeling of proteins in vitro. For all three cyclooctynes, thiol-yne addn. with reduced peptidylcysteines is responsible for most of the azide-independent polypeptide labeling. The identity of the reaction product was confirmed by LC-MS and NMR anal. Moreover, undesired thiol-yne reactions can be prevented by alkylating peptidylcysteine thiols with iodoacetamide (IAM). Since IAM is compatible with SPAAC, a more specific azide-dependent labeling is achieved by preincubating proteins contg. reduced cysteines with IAM.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XjtVWhsL0%253D&md5=091ab818d0b4582a4377e6a6a305a598
119. 119
  Poole, T. H.; Reisz, J. A.; Zhao, W.; Poole, L. B.; Furdui, C. M.; King, S. B. J. Am. Chem. Soc. 2014, 136, 6167
  [ ACS Full Text ], [ CAS], Google Scholar
  119
  Strained Cycloalkynes as New Protein Sulfenic Acid Traps
  Poole, Thomas H.; Reisz, Julie A.; Zhao, Weiling; Poole, Leslie B.; Furdui, Cristina M.; King, S. Bruce
  Journal of the American Chemical Society (2014), 136 (17), 6167-6170CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  Protein sulfenic acids are formed by the reaction of biol. relevant reactive oxygen species with protein thiols. Sulfenic acid formation modulates the function of enzymes and transcription factors either directly or through the subsequent formation of protein disulfide bonds. Identifying the site, timing, and conditions of protein sulfenic acid formation remains crucial to understanding cellular redox regulation. Current methods for trapping and analyzing sulfenic acids involve the use of dimedone and other nucleophilic 1,3-dicarbonyl probes that form covalent adducts with cysteine-derived protein sulfenic acids. As a mechanistic alternative, the present study describes highly strained bicyclo[6.1.0]nonyne (BCN) derivs. as concerted traps of sulfenic acids. These strained cycloalkynes react efficiently with sulfenic acids in proteins and small mols. yielding stable alkenyl sulfoxide products at rates >100x greater than 1,3-dicarbonyl reagents enabling kinetic competition with physiol. sulfur chem. Similar to the 1,3-dicarbonyl reagents, the BCN compds. distinguish the sulfenic acid oxoform from the thiol, disulfide, sulfinic acid, and S-nitrosated forms of cysteine while displaying an acceptable cell toxicity profile. The enhanced rates demonstrated by these strained alkynes identify them as new bioorthogonal probes that should facilitate the discovery of previously unknown sulfenic acid sites and their parent proteins.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXmtVegtL0%253D&md5=af7b13df6e6bd4101306df5be38bd88a
120. 120
  Ning, X.; Temming, R. P.; Dommerholt, J.; Guo, J.; Ania, D. B.; Debets, M. F.; Wolfert, M. A.; Boons, G.-J.; van Delft, F. L. Angew. Chem., Int. Ed. 2010, 49, 3065
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  120
  Protein Modification by Strain-Promoted Alkyne-Nitrone Cycloaddition
  Ning, Xinghai; Temming, Rinske P.; Dommerholt, Jan; Guo, Jun; Ania, Daniel B.; Debets, Marjoke F.; Wolfert, Margreet A.; Boons, Geert-Jan; van Delft, Floris L.
  Angewandte Chemie, International Edition (2010), 49 (17), 3065-3068, S3065/1-S3065/22CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
  The authors report a novel bioorthogonal reaction pair based on strain-promoted alkyne-nitrone cycloaddn. (SPANC) to give N-alkylated isoxazolines with exceptionally fast reaction kinetics. The new methodol. was used in a one-pot three-step protocol for the site-specific modification of peptides and proteins.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXkslSjs7Y%253D&md5=effbd9191246bdeccc84d091eba02a4b
121. 121
  Colombo, M.; Sommaruga, S.; Mazzucchelli, S.; Polito, L.; Verderio, P.; Galeffi, P.; Corsi, F.; Tortora, P.; Prosperi, D. Angew. Chem., Int. Ed. 2012, 51, 496
  [ Crossref], [ CAS], Google Scholar
  121
  Site-Specific Conjugation of ScFvs Antibodies to Nanoparticles by Bioorthogonal Strain-Promoted Alkyne-Nitrone Cycloaddition
  Colombo, Miriam; Sommaruga, Silvia; Mazzucchelli, Serena; Polito, Laura; Verderio, Paolo; Galeffi, Patrizia; Corsi, Fabio; Tortora, Paolo; Prosperi, Davide
  Angewandte Chemie, International Edition (2012), 51 (2), 496-499, S496/1-S496/17CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
  The authors demonstrated that strain-promoted azide-nitrone cycloaddn. (SPANC) allowed for the rapid and effective conjugation of proteins on nanoparticles functionalized with cyclooctyne ligands under mild conditions, provided that an N-terminal serine residue was introduced by mol. engineering. In particular, the application of SPANC to a scFv antibody against HER2 tumor marker resulted in its prompt immobilization on multifunctional nanoparticles (MFN), leading to water-stable bioengineered targeted MFN (TMFN), which exhibited a complete conservation of protein effectiveness in selectively targeting HER2 receptor in living cells. As the structural motif of scFv fragments is highly conserved, and other kinds of nanoparticles can be modified identically with the same polymer used herein, this approach is expected to be of general utility and may become a universal strategy for the development of a new generation of targeted nanoparticles.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhsFeqt7jJ&md5=f3d248326e6a8e4535d99242e4dc8067
122. 122
  Sanders, B. C.; Friscourt, F.; Ledin, P. A.; Mbua, N. E.; Arumugam, S.; Guo, J.; Boltje, T. J.; Popik, V. V.; Boons, G.-J. J. Am. Chem. Soc. 2011, 133, 949
  [ ACS Full Text ], [ CAS], Google Scholar
  122
  Metal-Free Sequential [3 + 2]-Dipolar Cycloadditions using Cyclooctynes and 1,3-Dipoles of Different Reactivity
  Sanders, Brian C.; Friscourt, Frederic; Ledin, Petr A.; Mbua, Ngalle Eric; Arumugam, Selvanathan; Guo, Jun; Boltje, Thomas J.; Popik, Vladimir V.; Boons, Geert-Jan
  Journal of the American Chemical Society (2011), 133 (4), 949-957CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  Although metal-free cycloaddns. of cyclooctynes and azides to give stable 1,2,3-triazoles have found wide utility in chem. biol. and material sciences, there is an urgent need for faster and more versatile bioorthogonal reactions. Here, it was shown that nitrile oxides and diazocarbonyl derivs. undergo facile 1,3-dipolar cycloaddns. with cyclooctynes. Cycloaddns. with diazocarbonyl derivs. exhibited similar kinetics as compared to azides, whereas the reaction rates of cycloaddns. with nitrile oxides were much faster. Nitrile oxides could conveniently be prepd. by direct oxidn. of the corresponding oximes with BAIB, and these conditions made it possible to perform oxime formation, oxidn., and cycloaddn. as a one-pot procedure. The methodol. was employed to functionalize the anomeric center of carbohydrates with various tags. Furthermore, oximes and azides provide an orthogonal pair of functional groups for sequential metal-free click reactions, and this feature makes it possible to multifunctionalize biomols. and materials by a simple synthetic procedure that does not require toxic metal catalysts.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhs1Srsb%252FL&md5=bb3c45c06a0ddd51b337e52ccf83afd3
123. 123
  Plougastel, L.; Koniev, O.; Specklin, S.; Decuypere, E.; Créminon, C.; Buisson, D.-A.; Wagner, A.; Kolodych, S.; Taran, F. Chem. Commun. 2014, 50, 9376
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  123
  4-Halogeno-sydnones for fast strain promoted cycloaddition with bicyclo-[6.1.0]-nonyne
  Plougastel, Lucie; Koniev, Oleksandr; Specklin, Simon; Decuypere, Elodie; Creminon, Christophe; Buisson, David-Alexandre; Wagner, Alain; Kolodych, Sergii; Taran, Frederic
  Chemical Communications (Cambridge, United Kingdom) (2014), 50 (66), 9376-9378CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
  New sydnone derivs. have been synthesized and screened for their capacity to undergo fast copper-free cycloaddn. reaction with bicyclo-[6.1.0]-nonyne to produce hydroxymethyldiazatricyclododecadienes, e. g., I. The influences of substitution in positions N-3 and C-4 of sydnones have been particularly studied leading to the identification of highly reactive partners for bio-orthogonal ligation reactions.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtVOnsrzO&md5=6f9ce153d24d861f1514e398f0f1994d
124. 124
  Stöckmann, H.; Neves, A. A.; Stairs, S.; Brindle, K. M.; Leeper, F. J. Org. Biomol. Chem. 2011, 9, 7303
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  124
  Exploring isonitrile-based click chemistry for ligation with biomolecules
  Stockmann Henning; Neves Andre A; Stairs Shaun; Brindle Kevin M; Leeper Finian J
  Organic & biomolecular chemistry (2011), 9 (21), 7303-5 ISSN:.
  We show here that isonitriles can perform click reactions with tetrazines in aqueous media, making them promising candidates for ligation reactions in chemical biology and polymer chemistry. This is the first time that a [4+1] cycloaddition has been used as a biocompatible ligation reaction.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3Mbgt1amug%253D%253D&md5=26eb8391000d79a5fef3ccabb9a91300
125. 125
  (a) Li, Y.; Pan, M.; Li, Y.; Huang, Y.; Guo, Q. Org. Biomol. Chem. 2013, 11, 2624
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  125a
  Thiol-yne radical reaction mediated site-specific protein labeling via genetic incorporation of an alkynyl-L-lysine analogue
  Li, Yiming; Pan, Man; Li, Yitong; Huang, Yichao; Guo, Qingxiang
  Organic & Biomolecular Chemistry (2013), 11 (16), 2624-2629CODEN: OBCRAK; ISSN:1477-0520. (Royal Society of Chemistry)
  Three N(ε)-alkynyl lysine derivs., H-Lys(CO2CH2C≡CH)-OH, H-Lys(CO2CH2CH2C≡CH)-OH and H-Lys(CO2CH2CH2CH2C≡CH)-OH, were synthesized and genetically encoded into proteins by a mutant PylRS-tRNA pair with high efficiencies. With these alkyne handles, site-specific dual labeling of proteins can be achieved via a bioorthogonal thiol-yne ligation reaction.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXksF2gsbk%253D&md5=d2a50bec20554216efca3b6919628a5e
  (b) Li, Y.; Yang, M.; Huang, Y.; Song, X.; Liu, L.; Chen, P. R. Chem. Sci. 2012, 3, 2766
  [ Crossref], [ CAS], Google Scholar
  125b
  Genetically encoded alkenyl-pyrrolysine analogues for thiol-ene reaction mediated site-specific protein labeling
  Li, Yiming; Yang, Maiyun; Huang, Yichao; Song, Xiaoda; Liu, Lei; Chen, Peng R.
  Chemical Science (2012), 3 (9), 2766-2770CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)
  A series of alkene-bearing pyrrolysine analogs were synthesized and subsequently incorporated into proteins at two sites by a mutant PylRS-tRNA pair with excellent efficiency. This strategy allowed the site-specific labeling of proteins carrying single or double genetically encoded alkene handles via bioorthogonal thiol-ene ligation reactions.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtFWns7zP&md5=ef1a6ad5a1c103b0593760d427fe9577
126. 126
  (a) Thomas, J. D.; Cui, H.; North, P. J.; Hofer, T.; Rader, C.; Burke, T. R. Bioconjugate Chem. 2012, 23, 2007
  [ ACS Full Text ], [ CAS], Google Scholar
  126a
  Application of Strain-Promoted Azide-Alkyne Cycloaddition and Tetrazine Ligation to Targeted Fc-Drug Conjugates
  Thomas, Joshua D.; Cui, Huiting; North, Patrick, J.; Hofer, Thomas; Rader, Christoph; Burke, Terrence R.
  Bioconjugate Chemistry (2012), 23 (10), 2007-2013CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
  We have previously described an approach whereby antibody Fc fragments harboring a single C-terminal selenocysteine residue (Fc-Sec) are directed against a variety of targets by changing the peptide or small mol. to which they are conjugated. In the present work, we describe methodol. for improving the efficacy of these Fc-Sec conjugates by incorporating cytotoxic drugs. The Fc-Sec protein is first programmed to target specific tumor cell types by attachment of a bifunctional linker that contains a "clickable" handle (e.g., cyclobutane or cyclooctyne) in addn. to a tumor cell-binding peptide or small mol. Following Fc-Sec conjugation, a cytotoxic warhead is then attached by cycloaddn. reactions of tetrazine or azide-contg. linker. To validate this approach, we used a model system in which folic acid (FA) is the targeting moiety and a disulfide-linked biotin moiety serves as a cytotoxic drug surrogate. We demonstrated successful targeting of Fc-Sec proteins to folate-receptor expressing tumor cells. Tetrazine ligation was found to be an efficient method for biotin "arming" of the folate-targeted Fc-Sec proteins. We also report novel bioconjugation methodologies that use [4 + 2] cycloaddn. reactions between tetrazines and cyclooctynes.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtlKlsbfP&md5=f6056b2a9f8ba428edd8785f95cbc2b9
  (b) Kele, P.; Mezö, G.; Achatz, D.; Wolfbeis, O. S. Angew. Chem., Int. Ed. 2009, 48, 344
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  126b
  Dual labeling of biomolecules by using click chemistry: a sequential approach
  Kele, Peter; Mezo, Gabor; Achatz, Daniela; Wolfdeis, Otto S.
  Angewandte Chemie, International Edition (2009), 48 (2), 344-347CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
  Dual labeling of model compds. was carried out by using copper-free and copper-mediated click chem. in a sequential manner. This method was used to introduce two labels onto biol. targets or nanoparticles, thus quickly converting them into fluorescence resonance energy transfer systems.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXhtFGns74%253D&md5=d831d2fd30cfbb51ff59099bc075ddab
127. 127
  (a) Plass, T.; Milles, S.; Koehler, C.; Szymański, J.; Mueller, R.; Wießler, M.; Schultz, C.; Lemke, E. A. Angew. Chem., Int. Ed. 2012, 51, 4166
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  127a
  Amino Acids for Diels-Alder Reactions in Living Cells
  Plass, Tilman; Milles, Sigrid; Koehler, Christine; Szymanski, Jedrzej; Mueller, Rainer; Wiessler, Manfred; Schultz, Carsten; Lemke, Edward A.
  Angewandte Chemie, International Edition (2012), 51 (17), 4166-4170, S4166/1-S4166/22CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
  The authors have genetically encoded unnatural amino acids (UAAs) for a biocompatible chem. in living cells that is orthogonal to the previously described cyclooctyne azide click chem. The basic utility of this new method for labeling of proteins in vivo was demonstrated in Escherichia coli. A particular focus of future work will be the development of more hydrophilic UAAs that facilitate easy washout of unincorporated UAA and thus high-contrast imaging. However, the authors were already able to show the high potential of genetically encoding a trans-cyclooctene deriv. for fluorescence imaging of specifically labeled proteins in mammalian cell culture. This approach will pave the way for labeling single protein sites with small fluorophores and other anal. or functional labels in physiol. relevant cells in the future.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XkvVKjs7c%253D&md5=40e0fe8d46aebd25280636e43185a0ec
  (b) Plass, T.; Milles, S.; Koehler, C.; Schultz, C.; Lemke, E. A. Angew. Chem., Int. Ed. 2011, 50, 3878
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  127b
  Genetically Encoded Copper-Free Click Chemistry
  Plass, Tilman; Milles, Sigrid; Koehler, Christine; Schultz, Carsten; Lemke, Edward A.
  Angewandte Chemie, International Edition (2011), 50 (17), 3878-3881, S3878/1-S3878/13CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
  One of the most potent functional groups for in vivo chem. has been genetically encoded into E. coli, and its basic utility for in vivo labeling as well as high-resoln. single-mol. measurements has been demonstrated. SPAAC (strain-promoted azide-alkyne cycloaddn.) chem. is now available to site-specifically and noninvasively modify proteins in living cells. As the tRNA'/pylRSA showed no obvious dependence on linker length (1 vs. 2), it is conceivable that slightly altered derivs., such as mono- and difluorinated cyclooctynes, and possibly bicyclonones, could be directly used in this system. Other enhanced cyclooctynes, such as dibenzocycloctynes, could pose substantial challenges to the synthetase and/or the host translational machinery owing to their larger size. As pylRS from M. mazei is orthogonal in a variety of eukaryotic organisms, we are now evaluating the transfer of this system to mammalian cells, where the technique would not only greatly expand our abilities to track proteins in living specimen but also to introduce other type of functional groups, such as cross-linkers or spin-labels for NMR spectroscopy and magnetic resonance imaging (MRI) in living specimens.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXkslChsLk%253D&md5=778aa80f13b1ea97bfce8236adc2cd4a
128. 128
  Hommersom, C. A.; Matt, B.; van der Ham, A.; Cornelissen, J. J. L. M.; Katsonis, N. Org. Biomol. Chem. 2014, 12, 4065
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  128
  Versatile post-functionalization of the external shell of cowpea chlorotic mottle virus by using click chemistry
  Hommersom, C. A.; Matt, B.; van der Ham, A.; Cornelissen, J. J. L. M.; Katsonis, N.
  Organic & Biomolecular Chemistry (2014), 12 (24), 4065-4069CODEN: OBCRAK; ISSN:1477-0520. (Royal Society of Chemistry)
  We present the modification of the outer protein shell of cowpea chlorotic mottle virus (CCMV) with linear and strained alkyne groups. These functionalized protein capsids constitute valuable platforms for post-functionalization via click chem. After modification, the integrity of the capsid and the reversible disassembly behavior are preserved.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXptVehsbs%253D&md5=7c1180fdfdecafd782d9e1d3ce3ae241
129. 129
  Wallace, S.; Chin, J. W. Chem. Sci. 2014, 5, 1742
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  129
  Strain-promoted sydnone bicyclo[6.1.0]nonyne cycloaddition
  Wallace, Stephen; Chin, Jason W.
  Chemical Science (2014), 5 (5), 1742-1744CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)
  The discovery and exploration of bioorthogonal chem. reactions and the biosynthetic incorporation of their components into biomols. for specific labeling is an important challenge. The reaction of a Ph sydnone 1,3-dipole with a bicyclononyne dipolarophile was described. This strain-promoted reaction proceeded without transition metal catalysis in aq. buffer, at physiol. temp., and pressure with a rate comparable to that of other bioorthogonal reactions. We demonstrate the quant. and specific labeling of a genetically encoded bicyclononyne with a sydnone fluorophore conjugate, demonstrating the utility of this approach for bioorthogonal protein labeling.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXlsFOrurw%253D&md5=73aa65d6137cbada75f1e467e1175647
130. 130
  Gattner, M. J.; Ehrlich, M.; Vrabel, M. Chem. Commun. 2014, 50, 12568
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  130
  Sulfonyl azide-mediated norbornene aziridination for orthogonal peptide and protein labeling
  Gattner, Michael J.; Ehrlich, Michael; Vrabel, Milan
  Chemical Communications (Cambridge, United Kingdom) (2014), 50 (83), 12568-12571CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
  We describe a new bioconjugation reaction based on the aziridination of norbornenes using electron-deficient sulfonyl azides. The reaction enables to attach various useful tags to peptides and proteins under mild conditions.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsVyhtr%252FJ&md5=0194aaf2cfa74290081d5a1bd97c5fb2
131. 131
  (a) Schneider, S.; Gattner, M. J.; Vrabel, M.; Flügel, V.; López-Carrillo, V.; Prill, S.; Carell, T. ChemBioChem 2013, 14, 2114
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  131a
  Structural Insights into Incorporation of Norbornene Amino Acids for Click Modification of Proteins
  Schneider, Sabine; Gattner, Michael J.; Vrabel, Milan; Fluegel, Veronika; Lopez-Carrillo, Veronica; Prill, Stefan; Carell, Thomas
  ChemBioChem (2013), 14 (16), 2114-2118CODEN: CBCHFX; ISSN:1439-4227. (Wiley-VCH Verlag GmbH & Co. KGaA)
  By using a Methanosarcina mazei pyrrolysine synthetase (PylRS) triple mutant (Y306G, Y384F, I405R) the incorporation of two new exo-norbornene-contg. pyrrolysine analogs was achieved. X-ray crystallog. anal. led to the identification of the crucial structural elements involved in substrate recognition by the evolved synthetase.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhsVeisLbN&md5=95fd7ac73dff6fc0137f186cc5f210b4
  (b) Han, H.-S.; Devaraj, N. K.; Lee, J.; Hilderbrand, S. A.; Weissleder, R.; Bawendi, M. G. J. Am. Chem. Soc. 2010, 132, 7838
  [ ACS Full Text ], [ CAS], Google Scholar
  131b
  Development of a bioorthogonal and highly efficient conjugation method for quantum dots using tetrazine-norbornene cycloaddn.
  Han, Hee-Sun; Devaraj, Neal K.; Lee, Jungmin; Hilderbrand, Scott A.; Weissleder, Ralph; Bawendi, Moungi G.
  Journal of the American Chemical Society (2010), 132 (23), 7838-7839CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  We present a bioorthogonal and modular conjugation method for efficient coupling of org. dyes and biomols. to quantum dots (QDs) using a norbornene-tetrazine cycloaddn. The use of noncoordinating functional groups combined with the rapid rate of the cycloaddn. leads to highly efficient conjugation. We have applied this method to the in situ targeting of norbornene-coated QDs to live cancer cells labeled with tetrazine-modified proteins.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXmt12lsLY%253D&md5=e78f454ff98b381b3e68c812074b9939
  (c) Kurra, Y.; Odoi, K. A.; Lee, Y.-J.; Yang, Y.; Lu, T.; Wheeler, S. E.; Torres-Kolbus, J.; Deiters, A.; Liu, W. R. Bioconjugate Chem. 2014, 25, 1730
  [ ACS Full Text ], [ CAS], Google Scholar
  131c
  Two Rapid Catalyst-Free Click Reactions for In Vivo Protein Labeling of Genetically Encoded Strained Alkene/Alkyne Functionalities
  Kurra, Yadagiri; Odoi, Keturah A.; Lee, Yan-Jiun; Yang, Yanyan; Lu, Tongxiang; Wheeler, Steven E.; Torres-Kolbus, Jessica; Deiters, Alexander; Liu, Wenshe R.
  Bioconjugate Chemistry (2014), 25 (9), 1730-1738CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
  Detailed kinetic analyses of inverse electron-demand Diels-Alder cycloaddn. and nitrilimine-alkene/alkyne 1,3-dipolar cycloaddn. reactions were conducted and the reactions were applied for rapid protein bioconjugation. When reacted with a tetrazine or a diaryl nitrilimine, strained alkene/alkyne entities including norbornene, trans-cyclooctene, and cyclooctyne displayed rapid kinetics. To apply these "click" reactions for site-specific protein labeling, five tyrosine derivs. that contain a norbornene, trans-cyclooctene, or cyclooctyne entity were genetically encoded into proteins in Escherichia coli using an engineered pyrrolysyl-tRNA synthetase-tRNAPylCUA pair. Proteins bearing these noncanonical amino acids were successively labeled with a fluorescein tetrazine dye and a diaryl nitrilimine both in vitro and in living cells.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsValsbvO&md5=a3871f4ff6141213fe8a43b7d86e7f96
132. 132
  (a) Wang, X. S.; Lee, Y.-J.; Liu, W. R. Chem. Commun. 2014, 50, 3176
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  132a
  The nitrilimine-alkene cycloaddition is an ultra rapid click reaction
  Wang, Xiaoshan Shayna; Lee, Yan-Jiun; Liu, Wenshe R.
  Chemical Communications (Cambridge, United Kingdom) (2014), 50 (24), 3176-3179CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
  The transient formation of nitrilimine in aq. conditions is greatly influenced by pH and chloride. In basic conditions (pH 10) with no chloride, a diarylnitrilimine precursor readily ionizes to form diarylnitrilimine that reacts almost instantly with an acrylamide-contg. protein and fluorescently labels it.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXjtFSnsb8%253D&md5=110e7d55cf4cdb059796fad9c551e83d
  (b) Lee, Y.-J.; Wu, B.; Raymond, J. E.; Zeng, Y.; Fang, X.; Wooley, K. L.; Liu, W. R. ACS Chem. Biol. 2013, 8, 1664
  [ ACS Full Text ], [ CAS], Google Scholar
  132b
  A Genetically Encoded Acrylamide Functionality
  Lee, Yan-Jiun; Wu, Bo; Raymond, Jeffrey E.; Zeng, Yu; Fang, Xinqiang; Wooley, Karen L.; Liu, Wenshe R.
  ACS Chemical Biology (2013), 8 (8), 1664-1670CODEN: ACBCCT; ISSN:1554-8929. (American Chemical Society)
  Nε-Acryloyl-L-lysine, a noncanonical amino acid with an electron deficient olefin, is genetically encoded in Escherichia coli using a pyrrolysyl-tRNA synthetase mutant in coordination with tRNACUAPyl. The acrylamide moiety is stable in cells, whereas it is active enough to perform a diverse set of unique reactions for protein modifications in vitro. These reactions include 1,4-addn., radical polymn., and 1,3-dipolar cycloaddn. A protein incorporated with Nε-acryloyl-L-lysine is efficiently modified with thiol-contg. nucleophiles at slightly alkali conditions, and the acrylamide moiety also allows rapid radical copolymn. of the same protein into a polyacrylamide hydrogel at physiol. pH. At physiol. conditions, the acrylamide functionality undergoes a fast 1,3-dipolar cycloaddn. reaction with diaryl nitrile imine to show turn-on fluorescence. The authors used this observation to demonstrate site-specific fluorescent labeling of proteins incorporated with Nε-acryloyl-L-lysine both in vitro and in living cells. This crit. development allows easy access to an array of modified proteins for applications where high specificity and reaction efficiency are needed.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXos1ygur8%253D&md5=521788a62a62cbd70ef7d306fe0d9045
  (c) Li, F.; Zhang, H.; Sun, Y.; Pan, Y.; Zhou, J.; Wang, J. Angew. Chem., Int. Ed. 2013, 52, 9700
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  132c
  Expanding the genetic code for photoclick chemistry in Escherichia coli, mammalian cells, and Arabidopsis thaliana
  Li, Fahui; Zhang, Hua; Sun, Yun; Pan, Yanchao; Zhou, Juanzuo; Wang, Jiangyun
  Angewandte Chemie, International Edition (2013), 52 (37), 9700-9704CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
  The unnatural amino acid N-ε-acryllysine (AcrK, I) was synthesized and incorporated into proteins in response to an amber stop codon in bacterial cells, mammalian cells, and plants. Genetic selection was used to develop an orthogonal tRNA/aminoacyl-tRNA synthetase pair that would selectively charge I in response to an amber codon. Diaryltetrazole II was chosen for photoclick protein labeling because it is highly reactive for photoclick reactions and sol. in water. I and II were used to label GFP and FtsZ proteins in Escherichia coli. I could be incorporated into EFGP protein in CHO cells. And in Arabidopsis thaliana, I could be incorporated into GFP-mCherry fusion proteins, which could subsequently be labeled with biotin-tetrazole using photoclick chem.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtFCrsrbM&md5=9bdbbb50fed317080bd23d293b9da520
  (d) Yu, Z.; Ohulchanskyy, T. Y.; An, P.; Prasad, P. N.; Lin, Q. J. Am. Chem. Soc. 2013, 135, 16766
  [ ACS Full Text ], [ CAS], Google Scholar
  132d
  Fluorogenic, Two-Photon-Triggered Photoclick Chemistry in Live Mammalian Cells
  Yu, Zhipeng; Ohulchanskyy, Tymish Y.; An, Peng; Prasad, Paras N.; Lin, Qing
  Journal of the American Chemical Society (2013), 135 (45), 16766-16769CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  The tetrazole-based photoclick chem. provides a powerful tool to image proteins in live cells. To extend photoclick chem. to living organisms with improved spatiotemporal control, here the authors report the design of naphthalene-based tetrazoles that can be efficiently activated by two-photon excitation with a 700 nm femtosecond pulsed laser. A water-sol., cell-permeable naphthalene-based tetrazole was identified that reacts with acrylamide with the effective two-photon cross-section for the cycloaddn. reaction detd. to be 3.8 GM. Furthermore, the use of this naphthalene-tetrazole for real-time, spatially controlled imaging of microtubules in live mammalian cells via the fluorogenic, two-photon-triggered photoclick chem. was demonstrated.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhs1yls7zL&md5=c004eb08406925ddb3b7bad043289916
  (e) Kaya, E.; Vrabel, M.; Deiml, C.; Prill, S.; Fluxa, V. S.; Carell, T. Angew. Chem., Int. Ed. 2012, 51, 4466
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  132e
  A Genetically Encoded Norbornene Amino Acid for the Mild and Selective Modification of Proteins in a Copper-Free Click Reaction
  Kaya, Emine; Vrabel, Milan; Deiml, Christian; Prill, Stefan; Fluxa, Viviana S.; Carell, Thomas
  Angewandte Chemie, International Edition (2012), 51 (18), 4466-4469, S4466/1-S4466/30CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
  Methods for the site-specific chem. modification of proteins are currently of immense importance for the synthesis of protein-hybrid compds. for pharmaceutical and diagnostic purposes. We have shown here that the generation of nitrile imines from the corresponding hydrazonoyl chlorides by direct HCl elimination under ambient conditions (pH 7.4) followed by reaction with a norbornene-contg. protein gives a fully active, modified protein. The click reaction with the norbornene-contg. protein proceeds with almost quant. yield in just 1 h at room temp. The ability to insert norbornene amino acids into proteins using the pyrrolysine system and the application of a special evolved synthetase now enables the reliable and efficient chem. modification of even sensitive proteins.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XktFyjsr0%253D&md5=fd96adc533070b1aed147a15cb106cba
  (f) Lang, K.; Davis, L.; Torres-Kolbus, J.; Chou, C.; Deiters, A.; Chin, J. W. Nat. Chem. 2012, 4, 298
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  132f
  Genetically encoded norbornene directs site-specific cellular protein labelling via a rapid bioorthogonal reaction
  Lang, Kathrin; Davis, Lloyd; Torres-Kolbus, Jessica; Chou, Chungjung; Deiters, Alexander; Chin, Jason W.
  Nature Chemistry (2012), 4 (4), 298-304CODEN: NCAHBB; ISSN:1755-4330. (Nature Publishing Group)
  The site-specific incorporation of bioorthogonal groups via genetic code expansion provides a powerful general strategy for site-specifically labeling proteins with any probe. However, the slow reactivity of the bioorthogonal functional groups that can be encoded genetically limits the utility of this strategy. We demonstrate the genetic encoding of a norbornene amino acid using the pyrrolysyl tRNA synthetase/tRNACUA pair in Escherichia coli and mammalian cells. We developed a series of tetrazine-based probes that exhibit turn-on' fluorescence on their rapid reaction with norbornenes. We demonstrate that the labeling of an encoded norbornene is specific with respect to the entire sol. E. coli proteome and thousands of times faster than established encodable bioorthogonal reactions. We show explicitly the advantages of this approach over state-of-the-art bioorthogonal reactions for protein labeling in vitro and on mammalian cells, and demonstrate the rapid bioorthogonal site-specific labeling of a protein on the mammalian cell surface.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhslGltr4%253D&md5=60615ac32a61d0d970b672b18058296d
  (g) Yu, Z.; Pan, Y.; Wang, Z.; Wang, J.; Lin, Q. Angew. Chem., Int. Ed. 2012, 51, 10600
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  132g
  Genetically Encoded Cyclopropene Directs Rapid, Photoclick-Chemistry-Mediated Protein Labeling in Mammalian Cells
  Yu, Zhipeng; Pan, Yanchao; Wang, Zhiyong; Wang, Jiangyun; Lin, Qing
  Angewandte Chemie, International Edition (2012), 51 (42), 10600-10604CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
  The authors report the synthesis of a stable cyclopropene amino acid, the characterization of its reactivity in the photoinduced cycloaddn. reaction with two tetrazoles, its site-specific incorporation into proteins both in E. coli and in mammalian cells, and its use in directing bioorthogonal labeling of proteins both in vitro and in vivo. The authors have demonstrated the genetic incorporation of a cyclopropene-contg. amino acid, CpK, site-specifically into target proteins, and the use of CpK as a bioorthogonal reporter for directing rapid (approx. two minutes) fluorescent labeling of the target protein in mammalian cells.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtlylsbnF&md5=ef89180e457b17a8afce60309811d481
133. 133
  Kamber, D. N.; Nazarova, L. A.; Liang, Y.; Lopez, S. A.; Patterson, D. M.; Shih, H.-W.; Houk, K. N.; Prescher, J. A. J. Am. Chem. Soc. 2013, 135, 13680
  [ ACS Full Text ], [ CAS], Google Scholar
  133
  Isomeric Cyclopropenes Exhibit Unique Bioorthogonal Reactivities
  Kamber, David N.; Nazarova, Lidia A.; Liang, Yong; Lopez, Steven A.; Patterson, David M.; Shih, Hui-Wen; Houk, K. N.; Prescher, Jennifer A.
  Journal of the American Chemical Society (2013), 135 (37), 13680-13683CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  1,3-Disubstituted and 3,3-disubstituted cyclopropenes I (R = H, Me; R1 = Me, H; R2 = Me2CHNH) and II (R = H, Me; R1 = Me, H) were prepd. as biocompatible labeling reagents. I and II (R = H; R1 = Me) underwent chemoselective inverse-electron Diels-Alder cycloaddns. with 1,2,4,5-tetrazines in aq. buffer, while I and II (R = Me; R1 = H) did not undergo Diels-Alder reaction in aq. solvent; I (R = H, Me; R1 = Me, H) underwent photochem. cycloaddn. with a nitrile imine generated in situ from a diaryltetrazole to give either a fluorescent cyclopropapyrazole III or the less fluorescent dihydropyridazine IV. The kinetics of inverse-electron Diels-Alder cycloaddns. of II (R = H, Me; R1 = Me, H) with 1,2,4,5-tetrazines in acetonitrile were detd.; transition state structures and activation barriers for inverse-electron Diels-Alder cycloaddns. were also calcd. Orthogonally reactive scaffolds such as cyclopropenes may provide improved methods for monitoring multicomponent processes in cells and organisms.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtlOksbbN&md5=38bab1a237b03b38c4bc986fe2d99b39
134. 134
  Yu, Z.; Lin, Q. J. Am. Chem. Soc. 2014, 136, 4153
  [ ACS Full Text ], [ CAS], Google Scholar
  134
  Design of Spiro[2.3]hex-1-ene, a Genetically Encodable Double-Strained Alkene for Superfast Photoclick Chemistry
  Yu, Zhipeng; Lin, Qing
  Journal of the American Chemical Society (2014), 136 (11), 4153-4156CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  Reactive yet stable alkene reporters offer a facile route to studying fast biol. processes via the cycloaddn.-based bioorthogonal reactions. Here, the authors report the design and synthesis of a strained spirocyclic alkene, spiro[2.3]hex-1-ene (Sph), for an accelerated photoclick chem., and its site-specific introduction into proteins via amber codon suppression using the wild-type pyrrolysyl-tRNA synthetase/tRNACUA pair. Because of its high ring strain and reduced steric hindrance, Sph exhibited fast reaction kinetics (k2 up to 34,000 M-1s-1) in the photoclick chem. and afforded rapid (<10 s) bioorthogonal protein labeling.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXjsVehs7k%253D&md5=732a856dd87427919e796627badf18ca
135. 135
  Darko, A.; Wallace, S.; Dmitrenko, O.; Machovina, M.; Mehl, R.; Chin, J. W.; Fox, J. Chem. Sci. 2014, 5, 3770
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  135
  Conformationally strained trans-cyclooctene with improved stability and excellent reactivity in tetrazine ligation
  Darko, Ampofo; Wallace, Stephen; Dmitrenko, Olga; Machovina, Melodie M.; Mehl, Ryan A.; Chin, Jason W.; Fox, Joseph M.
  Chemical Science (2014), 5 (10), 3770-3776CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)
  Computation has guided the design of conformationally-strained dioxolane-fused trans-cyclooctene (d-TCO) derivs. that display excellent reactivity in the tetrazine ligation. A water sol. deriv. of 3,6-dipyridyl-s-tetrazine reacts with d-TCO with a second order rate k2 366 000 (±15 000) M-1 s-1 at 25 °C in pure water. Furthermore, d-TCO derivs. can be prepd. easily, are accessed through diastereoselective synthesis, and are typically cryst. bench-stable solids that are stable in aq. soln., blood serum, or in the presence of thiols in buffered soln. GFP with a genetically encoded tetrazine-contg. amino acid was site-specifically labeled in vivo by a d-TCO deriv. The fastest bioorthogonal reaction reported to date [k2 3 300 000 (±40 000) M-1 s-1 in H2O at 25 °C] is described herein with a cyclopropane-fused trans-cyclooctene. D-TCO derivs. display rates within an order of magnitude of these fastest trans-cyclooctene reagents, and also display enhanced stability and aq. soly.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtFWhs7%252FP&md5=0c1df5e3978e2b05d7779d828f1928ef
136. 136
  (a) Wang, K.; Sachdeva, A.; Cox, D. J.; Wilf, N. W.; Lang, K.; Wallace, S.; Mehl, R. A.; Chin, J. W. Nat. Chem. 2014, 6, 393
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  136a
  Optimized orthogonal translation of unnatural amino acids enables spontaneous protein double-labeling and FRET
  Wang, Kaihang; Sachdeva, Amit; Cox, Daniel J.; Wilf, Nabil M.; Lang, Kathrin; Wallace, Stephen; Mehl, Ryan A.; Chin, Jason W.
  Nature Chemistry (2014), 6 (5), 393-403CODEN: NCAHBB; ISSN:1755-4330. (Nature Publishing Group)
  The ability to introduce different biophys. probes into defined positions in target proteins will provide powerful approaches for interrogating protein structure, function and dynamics. However, methods for site-specifically incorporating multiple distinct unnatural amino acids are hampered by their low efficiency. Here we provide a general soln. to this challenge by developing an optimized orthogonal translation system that uses amber and evolved quadruplet-decoding tRNAs to encode numerous pairs of distinct unnatural amino acids into a single protein expressed in Escherichia coli with a substantial increase in efficiency over previous methods. We also provide a general strategy for labeling pairs of encoded unnatural amino acids with different probes via rapid and spontaneous reactions under physiol. conditions. We demonstrate the utility of our approach by genetically directing the labeling of several pairs of sites in calmodulin with fluorophores and probing protein structure and dynamics by Foerster resonance energy transfer.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXmsVKqsbY%253D&md5=039742f70706d0e67f77d391ed2651e2
  (b) Sachdeva, A.; Wang, K.; Elliott, T.; Chin, J. W. J. Am. Chem. Soc. 2014, 136, 7785
  [ ACS Full Text ], [ CAS], Google Scholar
  136b
  Concerted, Rapid, Quantitative, and Site-Specific Dual Labeling of Proteins
  Sachdeva, Amit; Wang, Kaihang; Elliott, Thomas; Chin, Jason W.
  Journal of the American Chemical Society (2014), 136 (22), 7785-7788CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  Rapid, one-pot, concerted, site-specific labeling of proteins at genetically encoded unnatural amino acids with distinct small mols. at physiol. pH, temp., and pressure is an important challenge. Current approaches require sequential labeling, low pH, and typically days to reach completion, limiting their utility. We report the efficient, genetically encoded incorporation of alkyne- and cyclopropene-contg. amino acids at distinct sites in a protein using an optimized orthogonal translation system in E. coli. and quant., site-specific, one-pot, concerted protein labeling with fluorophores bearing azide and tetrazine groups, resp. Protein double labeling in aq. buffer at physiol. pH, temp., and pressure is quant. in 30 min.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXos1Wlurg%253D&md5=58e3a3c448deb78bf2a2e88ed57a8f9a
137. 137
  Floyd, N.; Vijayakrishnan, B.; Koeppe, J. R.; Davis, B. G. Angew. Chem., Int. Ed. 2009, 48, 7798
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  137
  Thiyl Glycosylation of Olefinic Proteins: S-Linked Glycoconjugate Synthesis
  Floyd, Nicola; Vijayakrishnan, Balakumar; Koeppe, Julia R.; Davis, Benjamin G.
  Angewandte Chemie, International Edition (2009), 48 (42), 7798-7802, S7798/1-S7798/72CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
  The authors describe the development of a convergent approach for the synthesis of a novel class of S-linked glycoconjugate proteins through the site-specific ligation of 1-glycosylthiols to proteins. The strategy exploits nonnatural amino acid incorporation for the introduction of L-homoallylglycine (L-Hag) into a protein and free-radical addn. hydrothiolation reactions, under conditions mild enough to retain protein activity throughout. In this way, Hag functions as a new tag combined here with a new modification as part of a general "tag-modify" strategy for synthetic-protein construction. While 1-thioglycoside formation by the free-radical addn. of 1-glycosylthiols to alkenes has been reported for the synthesis of small mols., to date this method has not been applied to the synthesis of S-linked glycoproteins or bioconjugates. The unique reactivity profile of L-Hag, with an olefinic sidechain compared to the natural amino acids characteristically found in proteins, allows for a chemoselective chem. reaction.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXht1ektL%252FN&md5=5de684052119bc60b41972eb8d09467a
138. 138
  Li, Q.; Dong, T.; Liu, X.; Lei, X. J. Am. Chem. Soc. 2013, 135, 4996
  [ ACS Full Text ], [ CAS], Google Scholar
  138
  A Bioorthogonal Ligation Enabled by Click Cycloaddition of o-Quinolinone Quinone Methide and Vinyl Thioether
  Li, Qiang; Dong, Ting; Liu, Xiaohui; Lei, Xiaoguang
  Journal of the American Chemical Society (2013), 135 (13), 4996-4999CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  There is an increasing interest in the use of bioorthogonal ligation to advance biomedical research through selective labeling of biomols. in living systems. Accordingly, discovering new reactions to expand the toolbox of bioorthogonal chem. is of particular interest to chem. biologists. Herein the authors report a new bioorthogonal ligation enabled by click hetero-Diels-Alder (HDA) cycloaddn. of in situ-generated o-quinolinone quinone methides and vinyl thioethers. This reaction is highly selective and proceeds smoothly under aq. conditions. The functionalized vinyl thioethers are small and chem. stable in vivo, making them suitable for use as bioorthogonal chem. reporters that can be effectively coupled to various biomols. The authors used this bioorthogonal ligation for site-specific labeling of proteins as well as imaging of bioactive small mols. inside live cells.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXksFSktrY%253D&md5=b446118ef6fa09c23d0f7070f8327d9c
139. 139
  Jouanno, L.-A.; Chevalier, A.; Sekkat, N.; Perzo, N.; Castel, H.; Romieu, A.; Lange, N.; Sabot, C.; Renard, P.-Y. J. Org. Chem. 2014, 79, 10353
  [ ACS Full Text ], [ CAS], Google Scholar
  139
  Kondrat'eva Ligation: Diels-Alder-Based Irreversible Reaction for Bioconjugation
  Jouanno, Laurie-Anne; Chevalier, Arnaud; Sekkat, Nawal; Perzo, Nicolas; Castel, Helene; Romieu, Anthony; Lange, Norbert; Sabot, Cyrille; Renard, Pierre-Yves
  Journal of Organic Chemistry (2014), 79 (21), 10353-10366CODEN: JOCEAH; ISSN:0022-3263. (American Chemical Society)
  Diversification of existing chemoselective ligations is required to efficiently access complex and well-defined biomol. assemblies with unique and valuable properties. The development and bioconjugation applications of a novel Diels-Alder-based irreversible site-specific ligation are reported. The strategy is based on a Kondrat'eva cycloaddn. between bioinert and readily functionalizable 5-alkoxyoxazoles and maleimides that readily react together under mild and easily tunable reaction conditions to afford a fully stable pyridine scaffold. The potential of this novel bioconjugation is demonstrated through the prepn. of fluorescent conjugates of biomols. and a novel Foerster resonance energy transfer (FRET)-based probe suitable for the in vivo detection and imaging of urokinase-like plasminogen activator (uPA), which is a key protease involved in cancer invasion and metastasis.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhslChtr%252FI&md5=ea5065a40a8c8fc9cbcfc9936ef2efa5
140. 140
  Engelsma, S. B.; Willems, L. I.; van Paaschen, C. E.; van Kasteren, S. I.; van der Marel, G. A.; Overkleeft, H. S.; Filippov, D. V. Org. Lett. 2014, 16, 2744
  [ ACS Full Text ], [ CAS], Google Scholar
  140
  Acylazetine as a Dienophile in Bioorthogonal Inverse Electron-Demand Diels-Alder Ligation
  Engelsma, Sander B.; Willems, Lianne I.; van Paaschen, Claudia E.; van Kasteren, Sander I.; van der Marel, Gijsbert A.; Overkleeft, Herman S.; Filippov, Dmitri V.
  Organic Letters (2014), 16 (10), 2744-2747CODEN: ORLEF7; ISSN:1523-7052. (American Chemical Society)
  A new bioorthogonal N-acylazetine tag, suitable for tetrazine mediated inverse electron-demand Diels-Alder conjugation, is developed. The tag is small and achiral. The authors demonstrate the usefulness of N-acylazetine-tetrazine based bioorthogonal chem. in two-step activity-based protein profiling. The performance of the new tetrazinophile in the labeling of catalytically active proteasome subunits was comparable to that of the more sterically demanding norbornene tag.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXnsFSlu7c%253D&md5=edc28f2e953876219470cd29a70f6ebf
141. 141
  (a) Yang, M.; Li, J.; Chen, P. R. Chem. Soc. Rev. 2014, 43, 6511
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  141a
  Transition metal-mediated bioorthogonal protein chemistry in living cells
  Yang, Maiyun; Li, Jie; Chen, Peng R.
  Chemical Society Reviews (2014), 43 (18), 6511-6526CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)
  A review. Considerable attention has been focused on improving the biocompatibility of Cu(I)-catalyzed azide-alkyne cycloaddn. (CuAAC), a hallmark of bioorthogonal reaction, in living cells. Besides creating copper-free versions of click chem. such as strain promoted azide-alkyne cycloaddn. (SPAAC), a central effort has also been made to develop various Cu(I) ligands that can prevent the cytotoxicity of Cu(I) ions while accelerating the CuAAC reaction. Meanwhile, addnl. transition metals such as palladium have been explored as alternative sources to promote a bioorthogonal conjugation reaction on cell surface, as well as within an intracellular environment. Furthermore, transition metal mediated chem. conversions beyond conjugation have also been utilized to manipulate protein activity within living systems. We highlight these emerging examples that significantly enriched our protein chem. toolkit, which will likely expand our view on the definition and applications of bioorthogonal chem.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtlOjt7vE&md5=bdb2ff120d8e0c77dfb30fe762d6c1f0
  (b) Chankeshwara, S. V.; Indrigo, E.; Bradley, M. Curr. Opin. Chem. Biol. 2014, 21, 128
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  141b
  Palladium-mediated chemistry in living cells
  Chankeshwara, Sunay V.; Indrigo, Eugenio; Bradley, Mark
  Current Opinion in Chemical Biology (2014), 21 (), 128-135CODEN: COCBF4; ISSN:1367-5931. (Elsevier B.V.)
  A review. Bioorthogonal metal-catalyzed chem. is the application of biocompatible transition metals to catalyze conventional synthetic org. chem. reactions within a biol. environment. Over the past decade, metals which were previously restricted to conventional org. synthesis have begun to be used in an increasing no. of biol. settings. This has been dominated by copper mediated catalysis of the azide-alkyne Huisgen cycloaddn. (1,3-dipolar addn.) chem. but other, less toxic, metals such as palladium are now beginning to establish themselves in the chem. biol./chem. medicine arenas. The potential of palladium mediated chem. in living systems now ranges from protein modifications to in cellulo synthesis or activation of drugs and suggests that palladium chem. has the potential to become a powerful tool. In this review we highlight recent advances in Pd-mediated reactions in living systems.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtleis7vJ&md5=835b177be06970103017428687f584e7
142. 142
  (a) Sasmal, P. K.; Streu, C. N.; Meggers, E. Chem. Commun. 2013, 49, 1581
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  142a
  Metal complex catalysis in living biological systems
  Sasmal, Pijus K.; Streu, Craig N.; Meggers, Eric
  Chemical Communications (Cambridge, United Kingdom) (2013), 49 (16), 1581-1587CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
  A review. This feature article discusses synthetic metal complexes that are capable of catalyzing chem. transformations in living organisms. Photodynamic therapy exemplifies what is probably the most established artificial catalytic process exploited in medicine, namely the photosensitized catalytic generation of cell-damaging singlet oxygen. Different redox catalysts have been designed over the last two decades to target a variety of redox alterations in cancer and other diseases. For example, pentaazamacrocyclic manganese(ii) complexes catalyze the dismutation of superoxide to O2 and H2O2in vivo and thus reduce oxidative stress in analogy to the native enzyme superoxide dismutase. Recently, piano-stool ruthenium and iridium complexes were reported to influence cellular redox homeostasis indirectly by catalytic glutathione oxidn. and catalytic transfer hydrogenation using the coenzyme NADH, resp. Over the last few years, significant progress was made towards the application of non-biol. reactions in living systems, ranging from the organoruthenium-catalyzed cleavage of alkylcarbamates and a gold-catalyzed intramol. hydroarylation to palladium-catalyzed Suzuki-Miyaura and Sonogashira cross-couplings within the cytoplasm or on the surface of living cells. The design of bioorthogonal catalyst/substrate pairs, which can passively diffuse into cells, combines the advantages of small mols. with catalysis and promises to provide exciting new tools for future chem. biol. studies.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhsFGqs7k%253D&md5=8fda2885942e7d87ff196d4f5f64c491
  (b) Antos, J. M.; Francis, M. B. Curr. Opin. Chem. Biol. 2006, 10, 253
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  142b
  Transition metal catalyzed methods for site-selective protein modification
  Antos, John M.; Francis, Matthew B.
  Current Opinion in Chemical Biology (2006), 10 (3), 253-262CODEN: COCBF4; ISSN:1367-5931. (Elsevier B.V.)
  A review. The broad utility of protein bioconjugates has created a need for new and diverse strategies for site-selective protein modification. In particular, chem. reactions that target alternative amino acid side chains or unnatural functional groups are emerging as a valuable complement to more commonly used lysine- and cysteine-based strategies. Considering their widespread use in org. synthesis, reactions catalyzed by transition metals could provide a particularly powerful set of transformations for the continued expansion of the bioconjugation toolkit. Recent efforts to apply transition metal catalysis to protein modification have resulted in new methods for protein crosslinking, tryptophan modification, tyrosine modification, reductive amination of protein amines, and unnatural amino acid labeling. These strategies have substantially expanded the synthetic flexibility of protein modification, and thus the range of applications for which bioconjugates can be used in chem. biol. and materials science.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28XltlKkt7c%253D&md5=6626f916736e808e8502459f30da9dd5
143. 143
  McFarland, J. M.; Francis, M. B. J. Am. Chem. Soc. 2005, 127, 13490
  [ ACS Full Text ], [ CAS], Google Scholar
  143
  Reductive Alkylation of Proteins Using Iridium Catalyzed Transfer Hydrogenation
  McFarland, Jesse M.; Francis, Matthew B.
  Journal of the American Chemical Society (2005), 127 (39), 13490-13491CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  An efficient transition metal catalyzed procedure for the reductive alkylation of proteins has been developed. Imines formed from the condensation of aldehydes (1 mM) with lysine residues and the N-terminus can be reduced efficiently by a [Cp*Ir(4,4'-dimethoxy-2,2'-bipyridine)(H2O)]SO4 catalyst in the presence of formate ions. The reaction proceeds readily at pH 7.4 in aq. phosphate buffer at temps. ranging from 22 to 37°, and reaches high levels of conversion for a no. of arom. aldehydes. UV expts. have confirmed that the catalyst does not bind to protein substrates. The utility of the reaction has been demonstrated through an efficient two-step procedure for the attachment of unfunctionalized poly(ethylene glycol) to protein targets.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXpslequrk%253D&md5=a1e9f5e3ce701be690116ba1ee113870
144. 144
  Tilley, S. D.; Francis, M. B. J. Am. Chem. Soc. 2006, 128, 1080
  [ ACS Full Text ], [ CAS], Google Scholar
  144
  Tyrosine-Selective Protein Alkylation Using π-Allylpalladium Complexes
  Tilley, S. David; Francis, Matthew B.
  Journal of the American Chemical Society (2006), 128 (4), 1080-1081CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  A new protein modification reaction has been developed based on a palladium-catalyzed allylic alkylation of tyrosine residues. This technique employs electrophilic π-allyl intermediates derived from allylic acetate and carbamate precursors and can be used to modify proteins in aq. soln. at room temp. To facilitate the detection of modified proteins using SDS-PAGE anal., a fluorescent allyl acetate was synthesized and coupled to chymotrypsinogen A and bacteriophage MS2. The tyrosine selectivity of the reaction was confirmed through trypsin digest anal. The utility of the reaction was demonstrated by using taurine-derived carbamates as water solubilizing groups that are cleaved upon protein functionalization. This soly. switching technique was used to install hydrophobic farnesyl and C17 chains on chymotrypsinogen A in water using little or no cosolvent. Following this, the C17 alkylated proteins were found to assoc. with lipid vesicles. In addn. to providing a new protein modification strategy targeting an underutilized amino acid side chain, this method provides convenient access to synthetic lipoproteins.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28XitVymsw%253D%253D&md5=8881b14279e96462847e868e6ede7c7e
145. 145
  Chen, S.; Li, X.; Ma, H. ChemBioChem 2009, 10, 1200
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  145
  New Approach for Local Structure Analysis of the Tyrosine Domain in Proteins by Using a Site-Specific and Polarity-Sensitive Fluorescent Probe
  Chen, Suming; Li, Xiaohua; Ma, Huimin
  ChemBioChem (2009), 10 (7), 1200-1207CODEN: CBCHFX; ISSN:1439-4227. (Wiley-VCH Verlag GmbH & Co. KGaA)
  Design and synthesis of a novel long-wavelength polarity-sensitive fluorescence probe, 6-[9-(diethylamino)-5-oxo-5 H-benzo[α]phenoxazin-2-yloxy]hex-2-enyl acetate, for the selective modification of tyrosine residues with the goal of providing local information on tyrosine domains in proteins, is reported. This probe comprises a polarity-sensitive Nile red fluorophore and an active π-allyl group that can form π-allylpalladium complexes and react selectively with tyrosine residues. Probe has the following features: 1) it has a long-wavelength emission of >550 nm, thanks to which interference from short-wavelength fluorescence from common biol. matrixes can be avoided; 2) the max. emission wavelength is sensitive only to polarity and not to pH or temp.; this allows the accurate detn. of local polarity; and 3) it is a neutral, uncharged mol., and does not disturb the overall charge of the labeled protein. With this probe the polarity and conformation changes of the Tyr108 domain in native and in acid- and heat-denatured bovine Cu/Zn superoxide dismutase were detected for the first time. It was found that the polarity of the Tyr108 domain hardly alters on acid denaturation between pH 4 and 9. However, heat denaturation caused the Tyr108 domain to be more hydrophobic, and was accompanied by an irreversible aggregation of the protein. In addn., the probe-binding expts. revealed that the surface of the protein becomes more hydrophobic after thermal denaturation; this can be ascribed to the formation of the more hydrophobic aggregates. This strategy might provide a general approach for studying the local environment changes of tyrosine domains in proteins under acid or heat denaturation conditions.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXmtVOntr4%253D&md5=e8597b98147adefc98ad29dc8a1a1cab
146. 146
  Cserép, G. B.; Herner, A.; Wolfbeis, O. S.; Kele, P. Bioorg. Med. Chem. Lett. 2013, 23, 5776
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  146
  Tyrosine specific sequential labeling of proteins
  Cserep, Gergely B.; Herner, Andras; Wolfbeis, Otto S.; Kele, Peter
  Bioorganic & Medicinal Chemistry Letters (2013), 23 (21), 5776-5778CODEN: BMCLE8; ISSN:0960-894X. (Elsevier B.V.)
  We report (a) on the synthesis of a long-wavelength fluorescent coumarin contg. an allyloxy acetate moiety, (b) the synthesis of two linkers contg. an allyloxy acetate and an alkyne or azide function, resp., and (c) the selective modification human serum albumin by a sequential method involving Pd(II) catalyzed modification of the phenolic side chain of tyrosine residues with an alkyne bearing linker and a subsequent azide-alkyne click reaction with an azide functionalized long-wavelength emitting coumarin dye. The method is likely to be applicable to various kinds of azido-modified fluorophores, and the Pd(II)-catalyzed modification of the tyrosines may also be used to introduce other kinds of tags. With these reagents, tyrosine specific modulation of proteins and peptides becomes possible either directly or in a sequential manner.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhsFaksLnL&md5=c6687310f4b084406df5153851c8db70
147. 147
  (a) Obermeyer, A. C.; Jarman, J. B.; Netirojjanakul, C.; El Muslemany, K.; Francis, M. B. Angew. Chem., Int. Ed. 2014, 53, 1057
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  147a
  Mild Bioconjugation Through the Oxidative Coupling of ortho-Aminophenols and Anilines with Ferricyanide
  Obermeyer, Allie C.; Jarman, John B.; Netirojjanakul, Chawita; El Muslemany, Kareem; Francis, Matthew B.
  Angewandte Chemie, International Edition (2014), 53 (4), 1057-1061CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
  Using a small-mol.-based screen, ferricyanide was identified as a mild and efficient oxidant for the coupling of anilines and o-aminophenols on protein substrates. This reaction is compatible with thiols and 1,2-diols, allowing its use in the creation of complex bioconjugates for use in biotechnol. and materials applications.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhvVykt7zE&md5=181fc5a090d96ebce0f4e7cc7f2b414f
  (b) Ji, A.; Ren, W.; Ai, H.-W. Chem. Commun. 2014, 50, 7469
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  147b
  A highly efficient oxidative condensation reaction for selective protein conjugation
  Ji, Ao; Ren, Wei; Ai, Hui-wang
  Chemical Communications (Cambridge, United Kingdom) (2014), 50 (56), 7469-7472CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
  We hereby report a mild and efficient coupling reaction between alkyl aldehydes and aryl diamines. In the presence of a Cu2+ or a Zn2+ ion, oxygen (O2) in air is able to promote the oxidative condensation of the two readily preparable functional groups, forming stable benzimidazole linkages in neutral aq. soln. at room temp. (RT). We demonstrated that the reaction could be utilized to label a T4 lysozyme protein contg. a chem. installed aryl diamine group with a fluorescent aldehyde dye mol. at 37 °C.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtVagur3N&md5=f5905e813ad3d2c97c1c8f7f2fcdaaea
  (c) Obermeyer, A. C.; Jarman, J. B.; Francis, M. B. J. Am. Chem. Soc. 2014, 136, 9572
  [ ACS Full Text ], [ CAS], Google Scholar
  147c
  N-Terminal Modification of Proteins with o-Aminophenols
  Obermeyer, Allie C.; Jarman, John B.; Francis, Matthew B.
  Journal of the American Chemical Society (2014), 136 (27), 9572-9579CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  The synthetic modification of proteins plays an important role in chem. biol. and biomaterials science. These fields provide a const. need for chem. tools that can introduce new functionality in specific locations on protein surfaces. In this work, an oxidative strategy is demonstrated for the efficient modification of N-terminal residues on peptides and N-terminal proline residues on proteins. The strategy uses o-aminophenols or o-catechols that are oxidized to active coupling species in situ using potassium ferricyanide. Peptide screening results have revealed that many N-terminal amino acids can participate in this reaction, and that proline residues are particularly reactive. When applied to protein substrates, the reaction shows a stronger requirement for the proline group. Key advantages of the reaction include its fast second-order kinetics and ability to achieve site-selective modification in a single step using low concns. of reagent. Although free cysteines are also modified by the coupling reaction, they can be protected through disulfide formation and then liberated after N-terminal coupling is complete. This allows access to doubly functionalized bioconjugates that can be difficult to access using other methods.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtVGlu77L&md5=ab16257753b27283d65e3d787b0bff7f
  (d) Seim, K. L.; Obermeyer, A. C.; Francis, M. B. J. Am. Chem. Soc. 2011, 133, 16970
  [ ACS Full Text ], [ CAS], Google Scholar
  147d
  Oxidative Modification of Native Protein Residues Using Cerium(IV) Ammonium Nitrate
  Seim, Kristen L.; Obermeyer, Allie C.; Francis, Matthew B.
  Journal of the American Chemical Society (2011), 133 (42), 16970-16976CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  A new protein modification strategy has been developed that is based on an oxidative coupling reaction that targets electron-rich amino acids. This strategy relies on cerium(IV) ammonium nitrate (CAN) as an oxidn. reagent and results in the coupling of tyrosine and tryptophan residues to phenylene diamine and anisidine derivs. The methodol. was first identified and characterized on peptides and small mols., and was subsequently adapted for protein modification by detg. appropriate buffer conditions. Using the optimized procedure, native and introduced solvent-accessible residues on proteins were selectively modified with polyethylene glycol (PEG) and small peptides. This unprecedented bioconjugation strategy targets these under-utilized amino acids with excellent chemoselectivity and affords good-to-high yields using low concns. of the oxidant and coupling partners, short reaction times, and mild conditions.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXht1GitLrO&md5=d32af6997266005a5bf1856e09eb8c0c
148. 148
  Antos, J. M.; Francis, M. B. J. Am. Chem. Soc. 2004, 126, 10256
  [ ACS Full Text ], [ CAS], Google Scholar
  148
  Selective tryptophan modification with rhodium carbenoids in aqueous solution
  Antos, John M.; Francis, Matthew B.
  Journal of the American Chemical Society (2004), 126 (33), 10256-10257CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  A new transition metal-based reaction has been developed for the selective modification of tryptophan residues on protein substrates. After activation of vinyl-substituted diazo compds. by Rh2(OAc)4, the resulting metallocarbenoid intermediates were found to modify indoles in aq. media despite competing reactions with water. Both N- and 2-substituted indole products were obsd. in the reaction. Following initial small-mol. studies, the reaction was performed on two protein substrates. Both myoglobin and subtilisin Carlsberg were modified readily in aq. soln., and the tryptophan selectivity of the reactions was confirmed through MS analyses of trypsin digest fragments. It was also demonstrated that myoglobin concns. as low as 10 μM still led to appreciable levels of modification. Reconstitution expts. confirmed that myoglobin retained its ability to bind heme following modification.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXmtVOjtrc%253D&md5=e4a855e9cdb8e6c6b44b321dd898106d
149. 149
  Antos, J. M.; McFarland, J. M.; Iavarone, A. T.; Francis, M. B. J. Am. Chem. Soc. 2009, 131, 6301
  [ ACS Full Text ], [ CAS], Google Scholar
  149
  Chemoselective Tryptophan Labeling with Rhodium Carbenoids at Mild pH
  Antos, John M.; McFarland, Jesse M.; Iavarone, Anthony T.; Francis, Matthew B.
  Journal of the American Chemical Society (2009), 131 (17), 6301-6308CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  Significant improvements have been made to a previously reported tryptophan modification method using rhodium carbenoids in aq. soln., allowing the reaction to proceed at pH 6-7. This technique is based on the discovery that N-(tert-butyl)hydroxylamine promotes indole modification with rhodium carbenoids over a broad pH range (2-7). This methodol. was demonstrated on peptide and protein substrates, generally yielding 40-60% conversion with excellent tryptophan chemoselectivity. The solvent accessibility of the indole side chains was a key factor in successful carbenoid addn., as demonstrated by conducting the reaction at temps. high enough to cause thermal denaturation of the protein substrate. Progress toward the expression of proteins bearing solvent accessible tryptophan residues as reactive handles for modification with rhodium carbenoids is also reported.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXksV2isrw%253D&md5=5c14c7fa813430af98264d990d2103ba
150. 150
  Kundu, R.; Ball, Z. T. Chem. Commun. 2013, 49, 4166
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  150
  Rhodium-catalyzed cysteine modification with diazo reagents
  Kundu, Rituparna; Ball, Zachary T.
  Chemical Communications (Cambridge, United Kingdom) (2013), 49 (39), 4166-4168CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
  A simple rhodium(II) complex catalyzes cysteine modification with diazo reagents. The reaction is marked by clean cysteine selectivity and mild reaction conditions. The resulting linkage is significantly more stable in human plasma serum, when compared to common maleimide reagents.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXmt1Cju78%253D&md5=9575bb0fbdd0b32c5af16b6d8182f6b7
151. 151
  Gillingham, D.; Fei, N. Chem. Soc. Rev. 2013, 42, 4918
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  151
  Catalytic X-H insertion reactions based on carbenoids
  Gillingham, Dennis; Fei, Na
  Chemical Society Reviews (2013), 42 (12), 4918-4931CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)
  A review. Catalyzed X-H insertion reactions into diazo compds. (X is any heteroatom) are a powerful yet underused class of transformations. The following review will explore the historical development of X-H insertion and give an up-to-date account of the metal catalysts most often employed, including an assessment of their strengths and weaknesses. Despite decades of development, recent work on enantioselective variants, as well as applying catalytic X-H insertion towards problems in chem. biol. indicate that this field has ample room for innovation.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXot1ersLk%253D&md5=7525f0a6d7724440ce89ce94f3f6e00c
152. 152
  On-Yee Chan, A.; Lui-Lui Tsai, J.; Kar-Yan Lo, V.; Li, G.-L.; Wong, M.-K.; Che, C.-M. Chem. Commun. 2013, 49, 1428
  [ Crossref], [ PubMed], Google Scholar
  There is no corresponding record for this reference.
153. 153
  Liu, C. C.; Schultz, P. G. Annu. Rev. Biochem. 2010, 79, 413
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  153
  Adding new chemistries to the genetic code
  Liu, Chang C.; Schultz, Peter G.
  Annual Review of Biochemistry (2010), 79 (), 413-444CODEN: ARBOAW; ISSN:0066-4154. (Annual Reviews Inc.)
  A review. The development of new orthogonal aminoacyl-tRNA synthetase/tRNA pairs has led to the addn. of approx. 70 unnatural amino acids (UAAs) to the genetic codes of Escherichia coli, yeast, and mammalian cells. These UAAs represent a wide range of structures and functions not found in the canonical 20 amino acids and thus provide new opportunities to generate proteins with enhanced or novel properties and probes of protein structure and function.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXpslShtrg%253D&md5=ce1f7de331d6a3b337678e7422c78239
154. 154
  (a) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B. Angew. Chem., Int. Ed. 2002, 41, 2596
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  154a
  A stepwise Huisgen cycloaddition process: copper(I)-catalyzed regioselective "ligation" of azides and terminal alkynes
  Rostovtsev, Vsevolod V.; Green, Luke G.; Fokin, Valery V.; Sharpless, K. Barry
  Angewandte Chemie, International Edition (2002), 41 (14), 2596-2599CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH)
  1,4-Disubstituted 1,2,3-triazoles I (R1 = PhCH2, PhCH2OCH2, 1-adamantyl, etc.; R2 = HO2C, Ph, PhOCH2, Et2NCH2, etc.) were readily and cleanly prepd. via highly efficient and regioselective copper(I)-catalyzed cycloaddn. of azides R1N3 with terminal alkynes R2C≡CH in 82-93% yields.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD38Xls1Ohsr4%253D&md5=4603664be6639353b5e70f19b9f8d59f
  (b) Tornoe, C. W.; Christensen, C.; Meldal, M. J. Org. Chem. 2002, 67, 3057
  [ ACS Full Text ], [ CAS], Google Scholar
  154b
  Peptidotriazoles on Solid Phase: [1,2,3]-Triazoles by Regiospecific Copper(I)-Catalyzed 1,3-Dipolar Cycloadditions of Terminal Alkynes to Azides
  Tornoe, Christian W.; Christensen, Caspar; Meldal, Morten
  Journal of Organic Chemistry (2002), 67 (9), 3057-3064CODEN: JOCEAH; ISSN:0022-3263. (American Chemical Society)
  The cycloaddn. of azides to alkynes is one of the most important synthetic routes to 1H-[1,2,3]-triazoles. This work reports a novel regiospecific copper(I)-catalyzed 1,3-dipolar cycloaddn. of terminal alkynes to azides on solid-phase. Primary, secondary, and tertiary alkyl azides, aryl azides, and an azido sugar were used successfully in the copper(I)-catalyzed cycloaddn. producing diversely 1,4-substituted [1,2,3]-triazoles in peptide backbones or side chains. The reaction conditions were fully compatible with solid-phase peptide synthesis on polar supports. The copper(I) catalysis is mild and efficient (>95% conversion and purity in most cases) and furthermore, the x-ray structure of 2-azido-2-methylpropanoic acid has been solved, to yield structural information on the 1,3-dipoles entering the reaction. Novel Fmoc-protected amino azides were prepd. from Fmoc-amino alcs. by Mitsunobu reaction.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD38XisVeks7w%253D&md5=6b3b805572783873952871f1b69f46dd
155. 155
  van Kasteren, S. I.; Kramer, H. B.; Jensen, H. H.; Campbell, S. J.; Kirkpatrick, J.; Oldham, N. J.; Anthony, D. C.; Davis, B. G. Nature 2007, 446, 1105
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  155
  Expanding the diversity of chemical protein modification allows post-translational mimicry
  van Kasteren, Sander I.; Kramer, Holger B.; Jensen, Henrik H.; Campbell, Sandra J.; Kirkpatrick, Joanna; Oldham, Neil J.; Anthony, Daniel C.; Davis, Benjamin G.
  Nature (London, United Kingdom) (2007), 446 (7139), 1105-1109CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)
  One of the most important current scientific paradoxes is the economy with which nature uses genes. In all higher animals studied, many fewer genes have been found than would have previously expected. The functional outputs of the eventual products of genes seem to be far more complex than the more restricted blueprint. In higher organisms, the functions of many proteins are modulated by post-translational modifications (PTMs). These alterations of amino-acid side chains lead to higher structural and functional protein diversity and are, therefore, a leading contender for an explanation for this seeming incongruity. Natural protein prodn. methods typically produce PTM mixts. within which function is difficult to dissect or control. Until now it has not been possible to access pure mimics of complex PTMs. Here the authors report a chem. tagging approach that enables the attachment of multiple modifications to bacterially expressed (bare) protein scaffolds: this approach allows reconstitution of functionally effective mimics of higher organism PTMs. By attaching appropriate modifications at suitable distances in the widely-used LacZ reporter enzyme scaffold, the authors created protein probes that included sensitive systems for detection of mammalian brain inflammation and disease. Through target synthesis of the desired modification, chem. provides a structural precision and an ability to retool with a chosen PTM in a manner not available to other approaches. In this way, combining chem. control of PTM with readily available protein scaffolds provides a systematic platform for creating probes of protein-PTM interactions. The authors therefore anticipate that this ability to build model systems will allow some of this gene product complexity to be dissected, with the aim of eventually being able to completely duplicate the patterns of a particular protein's PTMs from an in vivo assay into an in vitro system.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXksFeku7k%253D&md5=2cfb6409a93effd9f5a6fac9d8e5393e
156. 156
  Raliski, B. K.; Howard, C. A.; Young, D. D. Bioconjugate Chem. 2014, 25, 1916
  [ ACS Full Text ], [ CAS], Google Scholar
  156
  Site-Specific Protein Immobilization Using Unnatural Amino Acids
  Raliski, Benjamin K.; Howard, Christina A.; Young, Douglas D.
  Bioconjugate Chemistry (2014), 25 (11), 1916-1920CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
  Protein immobilization confers the advantages of biol. systems to a more chem. setting and has applications in catalysis, sensors, and materials development. While numerous immobilization techniques exist, it is optimal to develop a well-defined and chem. stable methodol. to allow for full protein function. This paper describes the utilization of unnatural amino acid technologies to introduce bioorthogonal handles in a site-specific fashion for protein immobilization. To develop this approach a range of solid-supports, org. linkers, and protein immobilization sites have been investigated using a GFP reporter system. Overall, a sepharose resin derivatized with propargyl alc. has afforded the highest yields of immobilized protein. Moreover, an unnatural amino acid residue protein context has been demonstrated, signifying a necessity to consider the protein site of immobilization. Finally, a resin-conferred stabilization was demonstrated in several org. solvents.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsl2ht73N&md5=a9bd97dac75c7d2eca300a07e6e7ed07
157. 157
  Boutureira, O.; D’Hooge, F.; Fernández-González, M.; Bernardes, G. J. L.; Sánchez-Navarro, M.; Koeppe, J. R.; Davis, B. G. Chem. Commun. 2010, 46, 8142
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  157
  Fluoroglycoproteins: ready chemical site-selective incorporation of fluorosugars into proteins
  Boutureira, Omar; D'Hooge, Francois; Fernandez-Gonzalez, Marta; Bernardes, Goncalo J. L.; Sanchez-Navarro, Macarena; Koeppe, Julia R.; Davis, Benjamin G.
  Chemical Communications (Cambridge, United Kingdom) (2010), 46 (43), 8142-8144CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
  A tag-and-modify strategy allows the practical synthesis of homogeneous fluorinated glyco-amino acids, peptides and proteins carrying a fluorine label in the sugar and allows access to first examples of directly radiolabeled ([18F]-glyco)proteins.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhtlentbvM&md5=e0047684173aba2d6adc8f4e6aea9606
158. 158
  Diaz Velazquez, H.; Ruiz Garcia, Y.; Vandichel, M.; Madder, A.; Verpoort, F. Org. Biomol. Chem. 2014, 12, 9350
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  158
  Water-soluble NHC-Cu catalysts: applications in click chemistry, bioconjugation and mechanistic analysis
  Diaz Velazquez, Heriberto; Ruiz Garcia, Yara; Vandichel, Matthias; Madder, Annemieke; Verpoort, Francis
  Organic & Biomolecular Chemistry (2014), 12 (46), 9350-9356CODEN: OBCRAK; ISSN:1477-0520. (Royal Society of Chemistry)
  Water-sol. copper(I) 2-imidazolidinylidene NHC complexes functionalized with sulfonate groups, [[1-Mes-3-[(CH2)nSO3K]C3H4N2]2Cu][PF6] (5, 6, n = 3, 4) and their 2-imidazolylidene counterparts [[1-Mes-3-[(CH2)nSO3K]C3H2N2]2Cu][PF6] (7, 8, n = 3, 4) were prepd. and evaluated for their catalytic activity in azide-alkyne click 1,3-dipolar cycloaddn., Staudinger amination and bioconjugation reactions. Copper(I)-catalyzed 1,3-dipolar cycloaddn. of azides and terminal alkynes (CuAAC), better known as "click" reaction, has triggered the use of 1,2,3-triazoles in bioconjugation, drug discovery, materials science and combinatorial chem. Here we report a new series of water-sol. catalysts based on N-heterocyclic carbene (NHC)-Cu complexes which are addnl. functionalized with a sulfonate group. The complexes show superior activity towards CuAAC reactions and display a high versatility, enabling the prodn. of triazoles with different substitution patterns. Addnl., successful application of these complexes in bioconjugation using unprotected peptides acting as DNA binding domains was achieved for the first time. Mechanistic insight into the reaction mechanism is obtained by means of state-of-the-art first principles calcns.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsVyrsLnM&md5=336505e23f6b177e85a0cdd9fce1b78e
159. 159
  (a) Besanceney-Webler, C.; Jiang, H.; Zheng, T.; Feng, L.; Soriano del Amo, D.; Wang, W.; Klivansky, L. M.; Marlow, F. L.; Liu, Y.; Wu, P. Angew. Chem., Int. Ed. 2011, 50, 8051
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  159a
  Increasing the Efficacy of Bioorthogonal Click Reactions for Bioconjugation: A Comparative Study
  Besanceney-Webler, Christen; Jiang, Hao; Zheng, Tianqing; Feng, Lei; Soriano del Amo, David; Wang, Wei; Klivansky, Liana M.; Marlow, Florence L.; Liu, Yi; Wu, Peng
  Angewandte Chemie, International Edition (2011), 50 (35), 8051-8056, S8051/1-S8051/19CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
  The parallel comparison of the bioorthogonal click reactions, namely the strain-promoted copper-free cycloaddn. and the ligand-accelerated CuAAC, verifies the great potential of the latter as a highly effective ligation tool for broad biol. applications. With the discovery of a new accelerating ligand for CuAAC, not only are kinetics that are faster than those of the known catalysts achieved, but more importantly, it allows for effective bioconjugation with suppressed cell cytotoxicity by further lowering CuI loading in the catalyst formulation. Although CuAAC requires multiple reagents to promote the reaction, which is more complicated compared to the copper-free click chem. where only one single reagent is used, the reaction conditions optimized here are the most effective in four biol. settings, i.e., labeling of recombinant glycoproteins, glycoproteins in crude cell lysates and on live cell surfaces, and in the enveloping layer of zebrafish embryos. An addnl. advantage of the bio-benign CuAAC is that it liberates the bioconjugation from the limitation where ligations could only be accomplished with azide-tagged biomols. Terminal alkyne residues can now also be incorporated into biomols. and detected in vivo. Overall, the reported ligand-accelerated CuAAC represents a powerful and highly adaptive bioconjugation tool for biologists, which holds great promise for further improvement with the discovery of more versatile catalyst systems.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXovVOhtbY%253D&md5=3d05dd94eceb1c53bd26c2bff1bffe0e
  (b) Kennedy, D. C.; McKay, C. S.; Legault, M. C. B.; Danielson, D. C.; Blake, J. A.; Pegoraro, A. F.; Stolow, A.; Mester, Z.; Pezacki, J. P. J. Am. Chem. Soc. 2011, 133, 17993
  [ ACS Full Text ], [ CAS], Google Scholar
  159b
  Cellular Consequences of Copper Complexes Used To Catalyze Bioorthogonal Click Reactions
  Kennedy, David C.; McKay, Craig S.; Legault, Marc C. B.; Danielson, Dana C.; Blake, Jessie A.; Pegoraro, Adrian F.; Stolow, Albert; Mester, Zoltan; Pezacki, John Paul
  Journal of the American Chemical Society (2011), 133 (44), 17993-18001CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  Copper toxicity is a crit. issue in the development of copper-based catalysts for copper(I)-catalyzed azide-alkyne cycloaddn. (CuAAC) reactions for applications in living systems. The effects and related toxicity of copper on mammalian cells are dependent on the ligand environment. Copper complexes can be highly toxic, can induce changes in cellular metab., and can be rapidly taken up by cells, all of which can affect their ability to function as catalysts for CuAAC in living systems. Herein, the authors have evaluated the effects of a no. of copper complexes that are typically used to catalyze CuAAC reactions on four human cell lines by measuring mitochondrial activity based on the metab. of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) to study toxicity, inductively coupled plasma mass spectrometry to study cellular uptake, and coherent anti-Stokes Raman scattering (CARS) microscopy to study effects on lipid metab. The authors find that ligand environment around copper influences all three parameters. Interestingly, for the Cu(II)-bis-L-histidine complex (Cu(his)2), cellular uptake and metabolic changes are obsd. with no toxicity after 72 h at micromolar concns. Furthermore, the authors show that under conditions where other copper complexes kill human hepatoma cells, Cu(I)-L-histidine is an effective catalyst for CuAAC labeling of live cells following metabolic incorporation of an alkyne-labeled sugar (Ac4ManNAl) into glycosylated proteins expressed on the cell surface. This result suggests that Cu(his)2 or derivs. thereof have potential for in vivo applications where toxicity as well as catalytic activity are crit. factors for successful bioconjugation reactions.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhtlCiurnJ&md5=ef9ed794ec654b5cd8aeb9220b14ba78
  (c) Hong, V.; Presolski, S. I.; Ma, C.; Finn, M. G. Angew. Chem., Int. Ed. 2009, 48, 9879
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  159c
  Analysis and Optimization of Copper-Catalyzed Azide-Alkyne Cycloaddition for Bioconjugation
  Hong, Vu; Presolski, Stanislav I.; Ma, Celia; Finn, M. G.
  Angewandte Chemie, International Edition (2009), 48 (52), 9879-9883, S9879/1-S9879/10CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
  Copper-catalyzed azide-alkyne cycloaddn. (CuAAC) has been optimized for use with biol. mols. The key development is the addn. of two reagents that allow ascorbate to be used as reducing agent while eliminating problems caused by copper ascorbate side reactions. The result is a robust, rapid, and convenient procedure for the modification of proteins, DNA, RNA, and other biomols. Sodium ascorbate is the preferred reducing agent for most applications, due to its convenience and effectiveness at generating the catalytically active Cu1 oxidn. state. Cu concns. should generally be between 50 and 100 μM. A fluorogenic or colorimetric assay, such as that enabled by a coumarin deriv. is strongly recommended for optimization of specific cases. At least five equiv. of THPTA (other water-sol. variants) relative to Cu should be employed. Aminoguanidine is a useful additive to intercept byproducts of ascorbate oxidn. that can covalently modify or crosslink proteins. Compatible buffers include phosphate, carbonate, or HEPES in the pH 6.5-8.0 range. Tris buffer should be avoided as it is a competitive and inhibitory ligand for Cu; sodium chloride (as in phosphate-buffered saline) up to 0.5 M can be used. Ascorbate should not be added to copper-contg. solns. in the absence of the ligand. As a matter of routine, the authors first mix CuSO4 with the ligand, add this mixt. to a soln. of the azide and alkyne substrates, and then initiate the CuAAC reaction by the addn. of sodium ascorbate to the desired concn. The Cu-THPTA catalyst in water is inhibited by excess alkyne, and so the procedure described here is useful for alkyne concns. less than approx. 5 mM.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXhsF2hsrnL&md5=2b85650bce37933080d02c417848f1e2
160. 160
  Kolodych, S.; Rasolofonjatovo, E.; Chaumontet, M.; Nevers, M.-C.; Créminon, C.; Taran, F. Angew. Chem., Int. Ed. 2013, 52, 12056
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  160
  Discovery of Chemoselective and Biocompatible Reactions Using a High-Throughput Immunoassay Screening
  Kolodych, Sergii; Rasolofonjatovo, Evelia; Chaumontet, Manon; Nevers, Marie-Claire; Creminon, Christophe; Taran, Frederic
  Angewandte Chemie, International Edition (2013), 52 (46), 12056-12060CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
  A method for high-throughput screening for identification and optimization of potential "click" reactions, particularly dipolar cycloaddns., using an immunoassay is described. Reactive groups attached to either homovanillic amide or histamine groups were reacted on nanomolar scale with a variety of metal catalysts; treatment with surface-linked anti(homovanillamide) monoclonal antibodies and antihistamine monoclonal antibodies in soln. led to a color change only when cycloadducts (contg. both homovanillamide and histamine tags) were formed and immobilized on the surface. Reactions that generated product were then optimized using the same assay format; four of the reactions were then performed using nontagged substrates. A rhodium-catalyzed cycloaddns. of pyridiniumacetates to nitriles to form imidazolopyridinecarboxylates, an iridium-catalyzed cycloaddn. of benzyl azide with bromoalkynes to form bromo-1,2,3-triazoles, a palladium-catalyzed and copper-mediated oxidative Heck reaction of a phenylsydnone with alkenes to yield alkenylsydnones, and a copper-catalyzed cycloaddn. of arylsydnones with alkynes to form arylpyrazoles were discovered using this method. In particular, copper-catalyzed cycloaddn. of arylsydnones with alkynes to form arylpyrazoles was found to be applicable to a variety of biol. relevant substrates, was performed successfully in human blood plasma, and was used to label bovine serum albumin with a fluorescent tag.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhs1WmtbvF&md5=fd99fb5fdf15e10d8b9078ce2dc90491
161. 161
  Tam, A.; Arnold, U.; Soellner, M. B.; Raines, R. T. J. Am. Chem. Soc. 2007, 129, 12670
  [ ACS Full Text ], [ CAS], Google Scholar
  161
  Protein Prosthesis: 1,5-Disubstituted[1,2,3]triazoles as cis-Peptide Bond Surrogates
  Tam, Annie; Arnold, Ulrich; Soellner, Matthew B.; Raines, Ronald T.
  Journal of the American Chemical Society (2007), 129 (42), 12670-12671CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  Here, 1,5-disubstituted[1,2,3]triazoles were assessed as cis-peptide bond surrogates. Ruthenium-catalyzed Huisgen's 1,3-dipolar cycloaddn. reaction of amino alkynes and azido acids was used to synthesize a variety of Xaa-1,5-triazole-Ala modules (Xaa = Asn, Ala) in moderate-to-high yields. Two of these modules, along with their 1,4-triazole regioisomers, were installed in a turn region of bovine pancreatic RNase (RNase A; 124 residues) by using expressed protein ligation. The resulting semisynthetic enzymes displayed full enzymic activity, indicating the maintenance of native structure. The 1,5-triazole surrogates instilled conformational stability that was comparable to that of Xaa-cis-Pro segments, whereas the 1,4-triazoles conferred markedly less stability. The stability conferred by both surrogates was independent of the Xaa residue, eliminating an uncertainty in protein design. The authors conclude that Xaa-1,5-triazole-Ala modules can serve as viable mimics of Xaa-cis-Pro segments. The possibility of synthesizing this surrogate by the ligation of fragments in situ and the emergence of biocompatible catalysts for that process portends its widespread use.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXhtFSmsLvK&md5=721929f0f64c5819562ad9e27209a82c
162. 162
  Li, J.; Chen, P. R. ChemBioChem 2012, 13, 1728
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  162
  Moving Pd-Mediated Protein Cross Coupling to Living Systems
  Li, Jie; Chen, Peng R.
  ChemBioChem (2012), 13 (12), 1728-1731CODEN: CBCHFX; ISSN:1439-4227. (Wiley-VCH Verlag GmbH & Co. KGaA)
  A review.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XpvVeksLo%253D&md5=8c6c6d6e7d4d5d0b53124e91a4319a2e
163. 163
  Li, N.; Lim, R. K. V.; Edwardraja, S.; Lin, Q. J. Am. Chem. Soc. 2011, 133, 15316
  [ ACS Full Text ], [ CAS], Google Scholar
  163
  Copper-Free Sonogashira Cross-Coupling for Functionalization of Alkyne-Encoded Proteins in Aqueous Medium and in Bacterial Cells
  Li, Nan; Lim, Reyna K.-V.; Edwardraja, Selvakumar; Lin, Qing
  Journal of the American Chemical Society (2011), 133 (39), 15316-15319CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  Bioorthogonal reactions suitable for functionalization of genetically or metabolically encoded alkynes, for example, copper-catalyzed azide-alkyne cycloaddn. reaction ("click chem."), have provided chem. tools to study biomol. dynamics and function in living systems. Despite its prominence in org. synthesis, copper-free Sonogashira cross-coupling reaction suitable for biol. applications has not been reported. In this work, the authors report the discovery of a robust aminopyrimidine-palladium(II) complex for copper-free Sonogashira cross-coupling that enables selective functionalization of a homopropargylglycine (HPG)-encoded ubiquitin protein in aq. medium. A wide range of arom. groups including fluorophores and fluorinated arom. compds. can be readily introduced into the HPG-contg. ubiquitin under mild conditions with good to excellent yields. The suitability of this reaction for functionalization of HPG-encoded ubiquitin in Escherichia coli was also demonstrated. The high efficiency of this new catalytic system should greatly enhance the utility of Sonogashira cross-coupling in bioorthogonal chem.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhtFOmsbbK&md5=80ce0c00b57ace6aee26caa4f5d6d19b
164. 164
  Lim, R. K. V.; Li, N.; Ramil, C. P.; Lin, Q. ACS Chem. Biol. 2014, 9, 2139
  [ ACS Full Text ], [ CAS], Google Scholar
  164
  Fast and Sequence-Specific Palladium-Mediated Cross-Coupling Reaction Identified from Phage Display
  Lim, Reyna K. V.; Li, Nan; Ramil, Carlo P.; Lin, Qing
  ACS Chemical Biology (2014), 9 (9), 2139-2148CODEN: ACBCCT; ISSN:1554-8929. (American Chemical Society)
  Fast and specific bioorthogonal reactions are highly desirable because they provide efficient tracking of biomols. that are present in low abundance and/or involved in fast dynamic process in living systems. Toward this end, classic strategy involves the optimization of substrate structures and reaction conditions in test tubes, testing their compatibility with biol. systems, devising synthetic biol. schemes to introduce the modified substrates into living cells or organisms, and finally validating the superior kinetics for enhanced capacity in tracking biomols. in vivo, a lengthy process often mired by unexpected results. Here, the authors report a streamlined approach in which the "microenvironment" of a bioorthogonal chem. reporter is exploited directly in biol. systems via phage-assisted interrogation of reactivity (PAIR) to optimize not only reaction kinetics but also specificity. Using the PAIR strategy, the authors identified a short alkyne-contg. peptide sequence showing fast kinetics (k2 = 13,000 ± 2000 M-1s-1) in a palladium-mediated cross-coupling reaction. Site-directed mutagenesis studies suggested that the residues surrounding the alkyne moiety facilitate the assembly of a key palladium-alkyne intermediate along the reaction pathway. When this peptide sequence was inserted into the extracellular domain of epidermal growth factor receptor (EGFR), this reactive sequence directed the specific labeling of EGFR in live mammalian cells.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtFCrur%252FM&md5=f4cf9c0c1ad66b7e5f26c164c3a56ae1
165. 165
  Hauke, S.; Best, M.; Schmidt, T. T.; Baalmann, M.; Krause, A.; Wombacher, R. Bioconjugate Chem. 2014, 25, 1632
  [ ACS Full Text ], [ CAS], Google Scholar
  165
  Two-Step Protein Labeling Utilizing Lipoic Acid Ligase and Sonogashira Cross-Coupling
  Hauke, Sebastian; Best, Marcel; Schmidt, Tobias T.; Baalmann, Mathis; Krause, Andre; Wombacher, Richard
  Bioconjugate Chemistry (2014), 25 (9), 1632-1637CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
  Labeling proteins in their natural settings with fluorescent proteins or protein tags often leads to problems. Despite the high specificity, these methods influence the natural functions due to the rather large size of the proteins used. Here the authors present a two-step labeling procedure for the attachment of various fluorescent probes to a small peptide sequence (13 amino acids) using enzyme-mediated peptide labeling in combination with palladium-catalyzed Sonogashira cross-coupling. The authors identified p-iodophenyl derivs. from a small library that can be covalently attached to a lysine residue within a specific 13-amino-acid peptide sequence by Escherichia coli lipoic acid ligase A (LplA). The derivatization with p-iodophenyl subsequently served as a reactive handle for bioorthogonal transition metal-catalyzed Sonogashira cross-coupling with alkyne-functionalized fluorophores on both the peptide as well as on the protein level. The authors' two-step labeling strategy combines high selectivity of enzyme-mediated labeling with the chemoselectivity of palladium-catalyzed Sonogashira cross-coupling.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsVSnsb%252FK&md5=9608ef7c5905f9956699d689adbf95be
166. 166
  Li, N.; Ramil, C. P.; Lim, R. K. V.; Lin, Q. ACS Chem. Biol. 2015, DOI: 10.1021/cb500649q
  [ ACS Full Text ], Google Scholar
  There is no corresponding record for this reference.
167. 167
  Li, J.; Lin, S.; Wang, J.; Jia, S.; Yang, M.; Hao, Z.; Zhang, X.; Chen, P. R. J. Am. Chem. Soc. 2013, 135, 7330
  [ ACS Full Text ], [ CAS], Google Scholar
  167
  Ligand-Free Palladium-Mediated Site-Specific Protein Labeling Inside Gram-Negative Bacterial Pathogens
  Li, Jie; Lin, Shixian; Wang, Jie; Jia, Shang; Yang, Maiyun; Hao, Ziyang; Zhang, Xiaoyu; Chen, Peng R.
  Journal of the American Chemical Society (2013), 135 (19), 7330-7338CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  Palladium, a key transition metal in advancing modern org. synthesis, mediates diverse chem. conversions including many carbon-carbon bond formation reactions between org. compds. However, expanding palladium chem. for conjugation of biomols. such as proteins, particularly within their native cellular context, is still in its infancy. Here the authors report the site-specific protein labeling inside pathogenic Gram-neg. bacterial cells via a ligand-free palladium-mediated cross-coupling reaction. Two rationally designed pyrrolysine analogs bearing an aliph. alkyne or an iodophenyl handle were first encoded in different enteric bacteria, which offered two facial handles for palladium-mediated Sonogashira coupling reaction on proteins within these pathogens. A GFP-based bioorthogonal reaction screening system was then developed, allowing evaluation of both the efficiency and the biocompatibility of various palladium reagents in promoting protein-small mol. conjugation. The identified simple compd. Pd(NO3)2 exhibited high efficiency and biocompatibility for site-specific labeling of proteins in vitro and inside living E. coli cells. This Pd-mediated protein coupling method was further used to label and visualize a Type-III Secretion (T3S) toxin-OspF in Shigella cells. The authors' strategy may be generally applicable for imaging and tracking various virulence proteins within Gram-neg. bacterial pathogens.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXntVWru74%253D&md5=4aeebc12f2f7c19fe35cabc2500566bc
168. 168
  Li, J.; Yu, J.; Zhao, J.; Wang, J.; Zheng, S.; Lin, S.; Chen, L.; Yang, M.; Jia, S.; Zhang, X.; Chen, P. R. Nat. Chem. 2014, 6, 352
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  168
  Palladium-triggered deprotection chemistry for protein activation in living cells
  Li, Jie; Yu, Juntao; Zhao, Jingyi; Wang, Jie; Zheng, Siqi; Lin, Shixian; Chen, Long; Yang, Maiyun; Jia, Shang; Zhang, Xiaoyu; Chen, Peng R.
  Nature Chemistry (2014), 6 (4), 352-361CODEN: NCAHBB; ISSN:1755-4330. (Nature Publishing Group)
  Employing small mols. or chem. reagents to modulate the function of an intracellular protein, particularly in a gain-of-function fashion, remains a challenge. In contrast to inhibitor-based loss-of-function approaches, methods based on a gain of function enable specific signalling pathways to be activated inside a cell. Here we report a chem. rescue strategy that uses a palladium-mediated deprotection reaction to activate a protein within living cells. We identify biocompatible and efficient palladium catalysts that cleave the propargyl carbamate group of a protected lysine analog to generate a free lysine. The lysine analog can be genetically and site-specifically incorporated into a protein, which enables control over the reaction site. This deprotection strategy is shown to work with a range of different cell lines and proteins. We further applied this biocompatible protection group/catalyst pair for caging and subsequent release of a crucial lysine residue in a bacterial Type III effector protein within host cells, which reveals details of its virulence mechanism.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXktlGntbo%253D&md5=31492f7589ae74bbf389b0400ddfa543
169. 169
  (a) Cheng, G.; Lim, R. K. V.; Li, N.; Lin, Q. Chem. Commun. 2013, 49, 6809
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  169a
  Storable palladacycles for selective functionalization of alkyne-containing proteins
  Cheng, Gang; Lim, Reyna K. V.; Li, Nan; Lin, Qing
  Chemical Communications (Cambridge, United Kingdom) (2013), 49 (60), 6809-6811CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
  We report the facile prepn. of palladacycles as storable arylpalladium(II) reagents from acetanilides via cyclopalladation. The palladacycles exhibit good stability in PBS buffer and are capable of functionalizing a metabolically encoded HPG-contg. protein, thus providing a new type of biocompatible organometallic reagent for selectively functionalizing the alkyne-encoded proteins.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtVCqur%252FI&md5=1bccc5ddd5a69c1ae41f78941bdf304f
  (b) Cheng, G.; Lim, R. K. V.; Ramil, C. P.; Lin, Q. Chem. Commun. 2014, 50, 11679
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  169b
  Storable N-phenylcarbamate palladacycles for rapid functionalization of an alkyne-encoded protein
  Cheng, Gang; Lim, Reyna K. V.; Ramil, Carlo P.; Lin, Qing
  Chemical Communications (Cambridge, United Kingdom) (2014), 50 (79), 11679-11682CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
  Here the authors report the synthesis of storable N-phenylcarbamate palladacycles, e.g., [EtOC(O)NC6H4-2-Pd(OTs)]2, that showed robust reactivity in the cross-coupling reaction with an alkyne-encoded protein, e.g., homopropargylglycine-encoded ubiquitin (Ub-Hpg), with a 2nd-order rate const. approaching 19,770 ± 930 M-1 s-1.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtlahtLzI&md5=8829434fa4db0fd92383bedef800cb37
170. 170
  Lin, Y. A.; Chalker, J. M.; Davis, B. G. ChemBioChem 2009, 10, 959
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  170
  Olefin Metathesis for Site-Selective Protein Modification
  Lin, Yuya A.; Chalker, Justin M.; Davis, Benjamin G.
  ChemBioChem (2009), 10 (6), 959-969CODEN: CBCHFX; ISSN:1439-4227. (Wiley-VCH Verlag GmbH & Co. KGaA)
  A review. Protein compatible olefin metathesis has emerged as a viable strategy for site-selective protein modification. This minireview traces its development from early peptide models and metathesis in water to its ultimate application to protein substrates. Prospects in chem. and biol. are also discussed. For a reaction to be generally useful for protein modification, it must be site-selective and efficient under conditions compatible with proteins: aq. media, low to ambient temp., and at or near neutral pH. To engineer a reaction that satisfies these conditions is not a simple task. Olefin metathesis is one of most useful reactions for carbon-carbon bond formation, but does it fit these requirements This minireview is an account of the development of olefin metathesis for protein modification. Highlighted below are examples of olefin metathesis in peptidic systems and in aq. media that laid the groundwork for successful metathesis on protein substrates. Also discussed are the opportunities in protein engineering for the genetic introduction of amino acids suitable for metathesis and the related challenges in chem. and biol.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXltVOlt7g%253D&md5=008e690219a6d333aabf7d43cc19e6f6
171. 171
  (a) Lin, Y. A.; Chalker, J. M.; Davis, B. G. J. Am. Chem. Soc. 2010, 132, 16805
  [ ACS Full Text ], [ CAS], Google Scholar
  171a
  Olefin Cross-Metathesis on Proteins: Investigation of Allylic Chalcogen Effects and Guiding Principles in Metathesis Partner Selection
  Lin, Yu-Ya A.; Chalker, Justin M.; Davis, Benjamin G.
  Journal of the American Chemical Society (2010), 132 (47), 16805-16811CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  Olefin metathesis has recently emerged as a viable reaction for chem. protein modification. The scope and limitations of olefin metathesis in bioconjugation, however, remain unclear. Herein the authors report an assessment of various factors that contribute to productive cross-metathesis on protein substrates. Sterics, substrate scope, and linker selection are all considered. It was discovered during this investigation that allyl chalcogenides generally enhance the rate of alkene metathesis reactions. Allyl selenides were exceptionally reactive olefin metathesis substrates, enabling a broad range of protein modifications not previously possible. The principles considered in this report are important not only for expanding the repertoire of bioconjugation but also for the application of olefin metathesis in general synthetic endeavors.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhtlyhtb%252FI&md5=1467f980a2500218483ad3de98a19b53
  (b) Lin, Y. A.; Chalker, J. M.; Floyd, N.; Bernardes, G. J. L.; Davis, B. G. J. Am. Chem. Soc. 2008, 130, 9642
  [ ACS Full Text ], [ CAS], Google Scholar
  171b
  Allyl Sulfides Are Privileged Substrates in Aqueous Cross-Metathesis: Application to Site-Selective Protein Modification
  Lin, Yuya A.; Chalker, Justin M.; Floyd, Nicola; Bernardes, Goncalo J. L.; Davis, Benjamin G.
  Journal of the American Chemical Society (2008), 130 (30), 9642-9643CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  Allyl sulfides undergo efficient cross-metathesis in aq. media with Hoveyda-Grubbs second generation catalyst. The high reactivity of allyl sulfides in cross-metathesis was exploited in the first examples of cross-metathesis on a protein surface. S-Allylcysteine was incorporated chem. into the protein, providing the requisite allyl sulfide handle. Preliminary efforts to genetically incorporate S-allylcysteine into proteins are also reported.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXnvF2gs7Y%253D&md5=a5d1a713c0c13d80961804b3bbfd9585
172. 172
  Chalker, J. M.; Lin, Y. A.; Boutureira, O.; Davis, B. G. Chem. Commun. 2009, 3714
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  172
  Enabling olefin metathesis on proteins: chemical methods for installation of S-allyl cysteine
  Chalker, Justin M.; Lin, Yuya A.; Boutureira, Omar; Davis, Benjamin G.
  Chemical Communications (Cambridge, United Kingdom) (2009), (25), 3714-3716CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
  Multiple, complementary methods are reported for the chem. conversion of cysteine to S-allylcysteine (Sac) on protein surfaces, a useful transformation for the exploration of olefin metathesis on proteins. These methods are the direct allylation of cysteine with allyl chloride and allylation by an allyl selenenyl sulfide rearrangement. The authors demonstrate that these methods are cysteine selective and provide metathesis-active Sac-contg. proteins. Moreover, the electrophilic allylation and allylic selenenyl sulfide rearrangement methods provide a single diastereomer of S-allylcysteine, unlike the nucleophilic addn. to dehydroalanine. Finally, the methods are mild, efficient, and easily accomplished without denaturing the protein.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXnslenu7g%253D&md5=fdd936e91817707c35f1f07ee1024d91
173. 173
  Lin, Y. A.; Davis, B. G. Beilstein J. Org. Chem. 2010, 6, 1219
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  173
  The allylic chalcogen effect in olefin metathesis
  Lin, Yuya A.; Davis, Benjamin G.
  Beilstein Journal of Organic Chemistry (2010), 6 (), 1219-1228, No. 140CODEN: BJOCBH; ISSN:1860-5397. (Beilstein-Institut zur Foerderung der Chemischen Wissenschaften)
  A review. Olefin metathesis has emerged as a powerful tool in org. synthesis. The activating effect of an allylic hydroxy group in metathesis has been known for more than 10 years, and many org. chemists have taken advantage of this pos. influence for efficient synthesis of natural products. Recently, the discovery of the rate enhancement by allyl sulfides in aq. cross-metathesis has allowed the first examples of such a reaction on proteins. This led to a new benchmark in substrate complexity for cross-metathesis and expanded the potential of olefin metathesis for other applications in chem. biol. The enhanced reactivity of allyl sulfide, along with earlier reports of a similar effect by allylic hydroxy groups, suggests that allyl chalcogens generally play an important role in modulating the rate of olefin metathesis. In this review, we discuss the effect of allylic chalcogens in olefin metathesis and highlight its most recent applications in synthetic chem. and protein modifications.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXjtlWruw%253D%253D&md5=269675c0ff77266a15cb7e277e321651
174. 174
  Lin, Y. A.; Boutureira, O.; Lercher, L.; Bhushan, B.; Paton, R. S.; Davis, B. G. J. Am. Chem. Soc. 2013, 135, 12156
  [ ACS Full Text ], [ CAS], Google Scholar
  174
  Rapid Cross-Metathesis for Reversible Protein Modifications via Chemical Access to Se-Allyl-selenocysteine in Proteins
  Lin, Yuya A.; Boutureira, Omar; Lercher, Lukas; Bhushan, Bhaskar; Paton, Robert S.; Davis, Benjamin G.
  Journal of the American Chemical Society (2013), 135 (33), 12156-12159CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  Cross-metathesis (CM) has recently emerged as a viable strategy for protein modification. Here, efficient protein CM has been demonstrated through biomimetic chem. access to Se-allyl selenocysteine (Seac), a metathesis-reactive amino acid substrate, via dehydroalanine. On-protein reaction kinetics reveal a rapid reaction with rate consts. of Seac-mediated-CM comparable or superior to off-protein rates of many current bioconjugations. This use of Se-relayed Seac CM on proteins has now enabled reactions with substrates (allyl GlcNAc, N-allyl acetamide) that were previously not possible for the corresponding sulfur analog. This CM strategy was applied to histone proteins to install a mimic of acetylated lysine (KAc, an epigenetic marker). The resulting synthetic H3 was successfully recognized by antibody that binds natural H3-K9Ac. Moreover, Cope-type selenoxide elimination allowed this putative marker (and function) to be chem. expunged, regenerating an H3 that can be rewritten to complete a chem. enabled "write (CM)-erase (ox)-rewrite (CM)" cycle.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtFOltr%252FL&md5=c2deb443d9e4d9db8f4040ff53c23943
175. 175
  Ai, H.-W.; Shen, W.; Brustad, E.; Schultz, P. G. Angew. Chem., Int. Ed. 2010, 49, 935
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  175
  Genetically encoded alkenes in yeast
  Ai, Hui-wang; Shen, Weijun; Brustad, Eric; Schultz, Peter G.
  Angewandte Chemie, International Edition (2010), 49 (5), 935-937, S935/1-S935/6CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
  The authors developed new tRNA/aminoacyl tRNA synthetase pairs that make possible the genetic incorporation of several alkene-contg. unnatural amino acids into proteins in eukaryotic cells. The orthogonal tRNA/aaRS pairs were evolved in Saccharomyces cerevisiae.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhtVGmsbc%253D&md5=dce69bcfcfaa069a417ca6622b0e653d
176. 176
  Ourailidou, M. E.; van der Meer, J.-Y.; Baas, B.-J.; Jeronimus-Stratingh, M.; Gottumukkala, A. L.; Poelarends, G. J.; Minnaard, A. J.; Dekker, F. J. ChemBioChem 2014, 15, 209
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  176
  Aqueous Oxidative Heck Reaction as a Protein-Labeling Strategy
  Ourailidou, Maria Eleni; van der Meer, Jan-Ytzen; Baas, Bert-Jan; Jeronimus-Stratingh, Margot; Gottumukkala, Aditya L.; Poelarends, Gerrit J.; Minnaard, Adriaan J.; Dekker, Frank J.
  ChemBioChem (2014), 15 (2), 209-212CODEN: CBCHFX; ISSN:1439-4227. (Wiley-VCH Verlag GmbH & Co. KGaA)
  An increasing no. of chem. reactions are being employed for bio-orthogonal ligation of detection labels to protein-bound functional groups. Several of these strategies, however, are limited in their application to pure proteins and are ineffective in complex biol. samples such as cell lysates. Here we present the palladium-catalyzed oxidative Heck reaction as a new and robust bio-orthogonal strategy for linking functionalized arylboronic acids to protein-bound alkenes in high yields and with excellent chemoselectivity even in the presence of complex protein mixts. from living cells. Advantageously, this reaction proceeds under aerobic conditions, whereas most other metal-catalyzed reactions require inert atm.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhvFOjtb%252FN&md5=6f915f26482ca3c5fb190e44f4dde824
177. 177
  Crich, D.; Subramanian, V.; Karatholuvhu, M. J. Org. Chem. 2009, 74, 9422
  [ ACS Full Text ], [ CAS], Google Scholar
  177
  Silver-Mediated Allylic Disulfide Rearrangement for Conjugation of Thiols in Protic Media
  Crich, David; Subramanian, Venkataraman; Karatholuvhu, Maheswaran
  Journal of Organic Chemistry (2009), 74 (24), 9422-9427CODEN: JOCEAH; ISSN:0022-3263. (American Chemical Society)
  Alkyl and aryl allyl disulfides are induced to undergo the desulfurative allylic rearrangement by silver nitrate in protic solvents at room temp., thereby removing the necessity for the use of phosphines as thiophilic reagents. The silver-mediated reaction functions at ambient temp. in protic solvents and in the absence of protecting groups.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXhsVWhsb7M&md5=18503822511d3f8a5a0dc2bbf0c5135a
178. 178
  Crich, D.; Zou, Y.; Brebion, F. J. Org. Chem. 2006, 71, 9172
  [ ACS Full Text ], [ CAS], Google Scholar
  178
  Sigmatropic Rearrangements as Tools for Amino Acid and Peptide Modification: Application of the Allylic Sulfur Ylide Rearrangement to the Preparation of Neoglycoconjugates and Other Conjugates
  Crich, David; Zou, Yekui; Brebion, Franck
  Journal of Organic Chemistry (2006), 71 (24), 9172-9177CODEN: JOCEAH; ISSN:0022-3263. (American Chemical Society)
  S-allyl and S-methallyl cysteines and cysteine-contg. dipeptide derivs. undergo ylide formation and [2,3] sigmatropic rearrangement reactions with stabilized and unstabilized diazo compds. and N-(diazoacetyl)glycosylamines in the presence of dirhodium tetraacetate to yield substituted S-allylated cysteines, cysteine-contg. peptides, and neoglycoconjugates such as I in 32-57% yields. Reaction of S-methallyl-Boc-L-Cys-L-Ala-L-Trp-OMe with Me(CH2)14COCHN2 gives a mixt. of products in low yield favoring insertion into the indole N-H bond.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28XhtFWju7nK&md5=ceb53807c5d8c03dbd6eedd40b343ab6
179. 179
  Croft, L. Nat. Chem. 2010, 2, 1009
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  179
  Prestige for palladium
  Croft, Laura
  Nature Chemistry (2010), 2 (12), 1009CODEN: NCAHBB; ISSN:1755-4330. (Nature Publishing Group)
  There is no expanded citation for this reference.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhsVOrsL%252FE&md5=591096d81d6775ecd87af2b880d5519e
180. 180
  Ojida, A.; Tsutsumi, H.; Kasagi, N.; Hamachi, I. Tetrahedron Lett. 2005, 46, 3301
  [ Crossref], [ CAS], Google Scholar
  180
  Suzuki coupling for protein modification
  Ojida, Akio; Tsutsumi, Hiroshi; Kasagi, Noriyuki; Hamachi, Itaru
  Tetrahedron Letters (2005), 46 (19), 3301-3305CODEN: TELEAY; ISSN:0040-4039. (Elsevier B.V.)
  Suzuki-coupling, a representative cross-coupling reaction between small mols., can proceed on a protein surface in aq. soln. under mild conditions. The modified protein produced by the coupling reaction maintained its native like structure and function. In addn., fluorescent dye appended-protein acts as a fluorescent biosensor.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXjtlKgu7c%253D&md5=e10fe7b7863166675da4ab0f805bf302
181. 181
  Kodama, K.; Fukuzawa, S.; Nakayama, H.; Kigawa, T.; Sakamoto, K.; Yabuki, T.; Matsuda, N.; Shirouzu, M.; Takio, K.; Tachibana, K.; Yokoyama, S. ChemBioChem 2006, 7, 134
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  181
  Regioselective carbon-carbon bond formation in proteins with palladium catalysis; new protein chemistry by organometallic chemistry
  Kodama, Koichiro; Fukuzawa, Seketsu; Nakayama, Hiroshi; Kigawa, Takanori; Sakamoto, Kensaku; Yabuki, Takashi; Matsuda, Natsuko; Shirouzu, Mikako; Takio, Koji; Tachibana, Kazuo; Yokoyama, Shigeyuki
  ChemBioChem (2006), 7 (1), 134-139CODEN: CBCHFX; ISSN:1439-4227. (Wiley-VCH Verlag GmbH & Co. KGaA)
  The authors have used a Mizoroki-Heck reaction for site-specific carbon-carbon bond formation in the Ras protein. This was performed by the following two steps: (1) the His6-fused Ras protein contg. 4-iodo-L-phenylalanine at position 32 (iF32-Ras-His) was prepd. by genetic engineering, and (2) the aryl iodide group on the iF32-Ras-His was coupled with vinylated biotin in the presence of a palladium catalyst. The biotinylation was confirmed by Western blotting and liq. chromatog.-mass spectrometry (LC-MS). The regioselectivity of the Mizoroki-Heck reaction was furthermore confirmed by LC-MS/MS anal. However, in addn. to the biotinylated product (bF32-Ras-His), a dehalogenated product (F32-Ras-His) was detected by LC-MS/MS. This dehalogenation resulted from the undesired termination of the Mizoroki-Heck reaction due to steric and electrostatic hindrance around residue 32. The biotinylated Ras showed binding activity for the Ras-binding domain as its downstream target, Raf-1, with no sign of decompn. This study is the first report of an application of organometallic chem. in protein chem.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28Xms1OmtQ%253D%253D&md5=cea92627c9ad74437baf24687f6acdb2
182. 182
  Kodama, K.; Fukuzawa, S.; Nakayama, H.; Sakamoto, K.; Kigawa, T.; Yabuki, T.; Matsuda, N.; Shirouzu, M.; Takio, K.; Yokoyama, S.; Tachibana, K. ChemBioChem 2007, 8, 232
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  182
  A new protein engineering approach combining chemistry and biology, part II, site-specific functionalization of proteins by organopalladium reactions
  Kodama, Koichiro; Fukuzawa, Seketsu; Nakayama, Hiroshi; Sakamoto, Kensaku; Kigawa, Takanori; Yabuki, Takashi; Matsuda, Natsuko; Shirouzu, Mikako; Takio, Koji; Yokoyama, Shigeyuki; Tachibana, Kazuo
  ChemBioChem (2007), 8 (2), 232-238CODEN: CBCHFX; ISSN:1439-4227. (Wiley-VCH Verlag GmbH & Co. KGaA)
  A new carbon-carbon bond has been regio-selectively introduced into a target position (position 32 or 174) of the Ras protein by two types of organopalladium reactions (Mizoroki-Heck and Sonogashira reactions). Reaction conditions were screened by using a model peptide, and the stability of the Ras protein under the reaction conditions was examd. by using the wild-type Ras protein. Finally, the iF-Ras proteins contg. a 4-iodo-L-phenylalanine residue were subjected to organopalladium reactions with vinylated or propargylated biotin. Site-specific biotinylations of the Ras protein were confirmed by Western blot and LC-MS/MS.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXht1Gnu7g%253D&md5=1b9f4349dc1b8fde4a34aea200f6dd83
183. 183
  Brustad, E.; Bushey, M. L.; Lee, J. W.; Groff, D.; Liu, W.; Schultz, P. G. Angew. Chem., Int. Ed. 2008, 47, 8220
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  183
  A genetically encoded boronate-containing amino acid
  Brustad, Eric; Bushey, Mark L.; Lee, Jae Wook; Groff, Dan; Liu, Wenshe; Schultz, Peter G.
  Angewandte Chemie, International Edition (2008), 47 (43), 8220-8223CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
  A biol. boronate: An orthogonal tRNA/aminoacyl-tRNA synthetase pair has been evolved for the genetic incorporation of a boronic acid into proteins. This amino acid has been used to purify proteins in a one-step scarless purifn. procedure as well as for the site-specific labeling of proteins using various boronic acid chemistries.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXht12htbrM&md5=049397eb711ad18bacd71746845d0acd
184. 184
  Chalker, J. M.; Wood, C. S. C.; Davis, B. G. J. Am. Chem. Soc. 2009, 131, 16346
  [ ACS Full Text ], [ CAS], Google Scholar
  184
  A Convenient Catalyst for Aqueous and Protein Suzuki-Miyaura Cross-Coupling
  Chalker, Justin M.; Wood, Charlotte S. C.; Davis, Benjamin G.
  Journal of the American Chemical Society (2009), 131 (45), 16346-16347CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  A phosphine-free palladium catalyst, generated from base, 4,6-dihydroxy-2-aminopyrimidine, and palladium acetate (I), is used as a catalyst for aq. Suzuki-Miyaura cross-coupling reactions of iodophenyl- and bromophenyl-contg. amino acids, an iodobenzylated protein, and iodoarenes with aryl boronic acids and an alkenylboronate. I mediates Suzuki-Miyaura coupling reactions to give hindered, ortho-substituted biaryls but does not react with or decomp. either peptides and proteins. The catalyst mediates Suzuki-Miyaura coupling reactions of brominated and iodinated Boc-tyrosines and S-(4-iodobenzyl)-Boc-glutathione, but does not catalyze Suzuki-Miyaura coupling of S-(4-iodobenzyl)-Boc-L-cysteine with phenylboronic acid; free cysteine or glutathione inhibit coupling reactions in the presence of I. A mutant of subtilisin Bacillus lentus (with a cysteine at residue 154 replacing a serine) is iodobenzylated at cysteine 154 and deactivated by benzylsulfonylation of the active site serine at residue 215; the inactivated and iodobenzylated product undergoes couplings with a variety of boronic acids in the presence of I in water in >95% conversions. The Suzuki-Miyaura couplings on the protein substrate are the first on a protein to proceed in useful conversions. Hydrophobic aryl and vinyl groups can be transferred to the protein surface without the aid of an org. solvent since the aryl- and vinylboronic acids used in the coupling are water-sol. as borate salts. The convenience and activity of this catalyst prompts use in both general synthesis and bioconjugation.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXhtlSlsLvF&md5=98a5115c8b3ea7175c6534fdf078e4a0
185. 185
  Spicer, C. D.; Davis, B. G. Chem. Commun. 2011, 47, 1698
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  185
  Palladium-mediated site-selective Suzuki-Miyaura protein modification at genetically encoded aryl halides
  Spicer, Christopher D.; Davis, Benjamin G.
  Chemical Communications (Cambridge, United Kingdom) (2011), 47 (6), 1698-1700CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
  Site-specific genetic incorporation of unnatural p-halophenylalanine amino acid residues as tags coupled with Pd(0)-mediated Suzuki-Miyuara modification has been enabled by discovery of an effective small mol. palladium scavenger.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXht1Wgs7s%253D&md5=265eee282a04f816f743c9cc3fe5de79
186. 186
  Spicer, C. D.; Triemer, T.; Davis, B. G. J. Am. Chem. Soc. 2012, 134, 800
  [ ACS Full Text ], [ CAS], Google Scholar
  186
  Palladium-Mediated Cell-Surface Labeling
  Spicer, Christopher D.; Triemer, Therese; Davis, Benjamin G.
  Journal of the American Chemical Society (2012), 134 (2), 800-803CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  Benign C-C bond formation at various sites in cell-surface channels has been achieved through Suzuki-Miyaura coupling of genetically positioned unnatural amino acids contg. aryl halide side chains. This enabled site-selective cell surface manipulation of Escherichia coli; the phosphine-free catalyst caused no cell death at required Pd loadings, suggesting future in vivo application of catalytic metal-mediated bond formation in more complex organisms.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhs1ers7zK&md5=f82eea8977542b5a69751a523cbaa6c6
187. 187
  Spicer, C. D.; Davis, B. G. Chem. Commun. 2013, 49, 2747
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  187
  Rewriting the bacterial glycocalyx via Suzuki-Miyaura cross-coupling
  Spicer, Christopher D.; Davis, Benjamin G.
  Chemical Communications (Cambridge, United Kingdom) (2013), 49 (27), 2747-2749CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
  Suzuki-Miyaura cross-coupling has been used to couple novel carbohydrate-based boronic acids, site-selectively, to the surface of E. coli at an unnatural amino acid. In this way, benign metal-catalyzed cellular switching allowed modulation of interactions with biomol. partners via prokaryotic O-glycosylation mimics.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXjslGntr4%253D&md5=2d6286f4710e8ee42ca04388d3851365
188. 188
  Ma, X.; Wang, H.; Chen, W. J. Org. Chem. 2014, 79, 8652
  [ ACS Full Text ], [ CAS], Google Scholar
  188
  N-Heterocyclic Carbene-Stabilized Palladium Complexes as Organometallic Catalysts for Bioorthogonal Cross-Coupling Reactions
  Ma, Xueji; Wang, Hangxiang; Chen, Wanzhi
  Journal of Organic Chemistry (2014), 79 (18), 8652-8658CODEN: JOCEAH; ISSN:0022-3263. (American Chemical Society)
  A small library of water-sol. N-heterocyclic carbene (NHC)-stabilized palladium complexes was prepd. and applied for cross-couplings of biomols. under mild conditions in water. Pd-NHC complexes bearing hydrophilic groups are efficient catalysts for the Suzuki-Miyaura coupling of various unnatural amino acids and proteins bearing p-iodophenyl functional groups. The authors further used this catalytic system for the rapid bioorthogonal labeling of proteins on the surfaces of mammalian cells. NHC-stabilized metal complexes have potential utility in cellular systems.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsVSns73J&md5=dc548e115000070b40b3a4c467d85fc3
189. 189
  Dumas, A.; Spicer, C. D.; Gao, Z.; Takehana, T.; Lin, Y. A.; Yasukohchi, T.; Davis, B. G. Angew. Chem., Int. Ed. 2013, 52, 3916
  [ Crossref], [ PubMed], [ CAS], Google Scholar
  189
  Self-Liganded Suzuki-Miyaura Coupling for Site-Selective Protein PEGylation
  Dumas, Anaelle; Spicer, Christopher D.; Gao, Zhanghua; Takehana, Tsuyoshi; Lin, Yuya A.; Yasukohchi, Tohru; Davis, Benjamin G.
  Angewandte Chemie, International Edition (2013), 52 (14), 3916-3921CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
  PEG-boronic acids, in the presence of simple Pd sources, are capable of acting as direct and effective Suzuki reagents in 70-98% yield. When combined with non-natural amino acids, they allow efficient and direct, site-selective PEGylation of proteins at predetd. positions under biol. compatible conditions without the need for exogenous ligands.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXjtVems7o%253D&md5=62a40ee8f1a8b5f5f2e4970c2d18add2

PDF [ 5MB]

Advances in Chemical Protein Modification

Article Views

Altmetric

Citations

1 Introduction

2 Transition Metal-Free Approaches

2.1 Classical Methods

Scheme 1

2.2 Modern Methods for Targeting Natural Amino Acids

2.2.1 Lysine and N-Terminus

Scheme 2

2.2.2 Tyrosine

Scheme 3

2.2.3 Cysteine

Scheme 4

Scheme 5

Scheme 6

Scheme 7

Scheme 8

Scheme 9

2.2.4 Disulfides

Scheme 10

2.3 Modern Methods for Targeting Unnatural Amino Acids

2.3.1 Carbonyl Handles

Scheme 11

2.3.2 Alkynes, Alkenes, and Dipole Handles

Scheme 12

Scheme 13

Scheme 14

Scheme 15

Scheme 16

3 Transition Metal-Mediated Approaches

3.1 Methods for Targeting Natural Amino Acids

3.1.1 Lysine and Tyrosine with Iridium and Palladium Complexes

Scheme 17

3.1.2 Natural Residues with Rhodium and Gold Complexes

Scheme 18

3.2 Methods for Targeting Unnatural Amino Acids

3.2.1 Azides, Sydnones, Alkynes, and Alkenes

Scheme 19

Scheme 20

Scheme 21

3.2.2 Aryl Halides and Boronates

Scheme 22

Scheme 23

4 Conclusion

Acknowledgment

References

Cited By

Abstract

Scheme 1

Scheme 2

Scheme 3

Scheme 4

Scheme 5

Scheme 6

Scheme 7

Scheme 8

Scheme 9

Scheme 10

Scheme 11

Scheme 12

Scheme 13

Scheme 14

Scheme 15

Scheme 16

Scheme 17

Scheme 18

Scheme 19

Scheme 20

Scheme 21

Scheme 22

Scheme 23

References

STEP 1:

STEP 2:

OOPS

This website uses cookies to improve your user experience. By continuing to use the site, you are accepting our use of cookies. Read the ACS privacy policy.