ACS Publications. Most Trusted. Most Cited. Most Read
Quick View

OR SEARCH CITATIONS

My Activity
Publications
CONTENT TYPES

Figure 1Loading Img
Download Hi-Res ImageDownload to MS-PowerPointCite This:Crystal Growth & Design 2021, 21, 3, 1424-1427
RETURN TO ISSUEPREVCommunicationNEXT

Noncovalent Protein–Pseudorotaxane Assembly Incorporating an Extended Arm Calix[8]arene with α-Helical Recognition Properties

  • Niamh M. Mockler
    Niamh M. Mockler
    School of Chemistry, National University of Ireland Galway, University Road, Galway, H91 TK33, Ireland
    More by Niamh M. Mockler
  • , 
  • Kiefer O. Ramberg
    Kiefer O. Ramberg
    School of Chemistry, National University of Ireland Galway, University Road, Galway, H91 TK33, Ireland
    More by Kiefer O. Ramberg
  • , 
  • Francesca Guagnini
    Francesca Guagnini
    School of Chemistry, National University of Ireland Galway, University Road, Galway, H91 TK33, Ireland
    More by Francesca Guagnini
  • , 
  • Colin L. Raston
    Colin L. Raston
    Flinders Institute for Nanoscale Science and Technology, College of Science and Engineering, Flinders University, Bedford Park, South 5042, Australia
    More by Colin L. Raston
    Orcidhttp://orcid.org/0000-0003-4753-0079
  • , and 
  • Peter B. Crowley*
    Peter B. Crowley
    School of Chemistry, National University of Ireland Galway, University Road, Galway, H91 TK33, Ireland
    *Email: [email protected]. Phone: +353 91 49 24 80.
    More by Peter B. Crowley
    Orcidhttp://orcid.org/0000-0002-5365-0096
Cite this: Cryst. Growth Des. 2021, 21, 3, 1424–1427
Publication Date (Web):February 8, 2021
https://doi.org/10.1021/acs.cgd.0c01717

Copyright © 2022 The Authors. Published by American Chemical Society. This publication is licensed under

CC-BY 4.0.
  • Open Access

Article Views

1250

Altmetric

-

Citations

7
LEARN ABOUT THESE METRICS
PDF (3 MB)
Get e-Alerts
Supporting Info (1)»
SUBJECTS:

Abstract

High Resolution Image
Download MS PowerPoint Slide

Water-soluble, anionic calix[n]arenes are useful receptors for protein recognition and assembly. For example, sulfonato-calix[8]arene (sclx8) can encapsulate proteins and direct their assembly into porous frameworks. In this work, we turned our attention to an “extended arm” calixarene with 16 phenyl rings. We hypothesized that this larger receptor would have increased capacity for protein masking/encapsulation. A cocrystal structure of p-benzyl-sulfonato-calix[8]arene (b-sclx8) and cytochrome c (cyt c) revealed a surprising assembly. A pseudorotaxane comprising a stack of three b-sclx8 molecules threaded by polyethylene glycol (PEG) was bound to the protein. The trimeric b-sclx8 stack, a tubelike structure with a highly charged surface, mediated assembly via a new mode of protein recognition. The calixarene stack presents four hydrophobic grooves, each of which binds to one cyt c by accommodating the N-terminal α-helix. This unprecedented binding mode suggests new possibilities for supramolecular protein chemistry.

This publication is licensed under

CC-BY 4.0.
  • cc licence
  • by licence

Synopsis

Extended arm calix[8]arene self-assembles as a trimeric stack with hydrophobic grooves that accommodate an α-helix of cytochrome c. The calixarene stack is threaded by polyethylene to yield a pseudorotaxane.

The complex topology of protein surfaces presents ample opportunity for recognition by synthetic molecules, resulting in diverse functions. (1−4) Small molecules that occupy α-helical-binding grooves on a protein surface can be applied to inhibit protein–protein interactions. (1) Supramolecular receptors, such as cucurbit[n]urils (5−8) and calix[n]arenes, (9−20) that target specific side chains have applications in controlled protein assembly and noncovalent PEGylation of biopharmaceuticals. Water-soluble, anionic calixarenes have useful recognition properties arising from their affinity for cationic residues (Lys, Arg). The commercially available sulfonato-calix[n]arenes (sclxn) are gaining traction as off-the-shelf mediators of protein assembly. Acting as “molecular glues”, sclxn can mediate protein oligomerization and direct the packing of protein frameworks. (14,16,18,20) Such frameworks provide a foundation for biodegradable and biocompatible materials with potential applications in drug delivery, catalysis, protein-based coatings, and more. (2,3,21) Additionally, calixarenes can be employed in mechanically interlocked molecules (MIMs), including rotaxanes and catenanes. (22−26) Consequently, there is opportunity to generate MIMs with protein recognition capacity, providing new types of biohybrid materials and/or molecular machines. Here, we describe the protein recognition and assembly activity of p-benzyl-sulfonato-calix[8]arene (b-sclx8, Figure 1), an extended arm calixarene. (27)

Figure 1

Figure 1. Sulfonato-calix[8]arene (sclx8) and p-benzyl-sulfonato-calix[8]arene (b-sclx8).

High Resolution Image
Download MS PowerPoint Slide

Crystal structures of cationic proteins in complex with differently functionalized calix[4]arenes, (9,12,13,15,16,19) calix[6]arenes, (11,16,17) and calix[8]arenes (14,16,18) have highlighted the advantages of larger calixarene hosts. The inherent flexibility of sclx6 and sclx8 compared to the bowl-shaped sclx4 facilitates topological molding to protein surfaces and greater surface coverage. Our recently reported crystal structures have established that sclx8 (Figure 1) can mask up to ∼30% of the cytochrome c (cyt c) surface. (14) Autoregulated assembly of cyt c was achieved, with tetramerization at 1 equiv and oligomer disassembly at ≥3 equiv of sclx8. (14) Furthermore, crystalline frameworks of cyt c and sclx8 with varying porosities and up to ∼5 nm pore diameter were obtained, as a function of the calixarene concentration. (14,18) Cyt c-sclx8 frameworks were amenable to crystal engineering, with the introduction of a small molecule effector facilitating framework duplication. (18) Considering these results, we were interested to test how a larger sclx8 derivative, b-sclx8, might manipulate the assembly of cyt c. With a solvent accessible surface area (ASA) of 2400 Å2, b-sclx8 was expected to mask a larger portion of cyt c than sclx8 (ASA = 1600 Å2). Complex formation between b-sclx8 and cyt c was studied by NMR spectroscopy and X-ray crystallography, the latter revealing an unexpected biohybrid assembly.

Initially, we investigated the interactions of cyt c and b-sclx8 via 1H–15N HSQC-monitored titrations in 20 mM sodium acetate, 50 mM NaCl at pH 5.6. Backbone amide chemical shift perturbations were observed at 2 equiv of b-sclx8. The resonances of Ala3, Lys4, Lys5, Thr12, and Lys86 were perturbed, suggesting that b-sclx8 interacted with part of the known calixarene binding patch on cyt c (Figure 2). (9,11−15,17−19) At ≥ 4 equiv of b-sclx8, the sample precipitated, resulting in signal loss in the 1H–15N HSQC spectrum and precluding further analysis. Therefore, we turned to crystallography to investigate the protein–calixarene interaction in more detail.

Figure 2

Figure 2. Overlaid regions of the 1H–15N HSQC spectra of cyt c in the absence (black contours) and presence of 2 (red) or 4 (blue) equiv of b-sclx8, in 20 mM sodium acetate and 50 mM NaCl, pH 5.6. Note the signal loss at 4 equiv of b-sclx8 due to sample precipitation.

High Resolution Image
Download MS PowerPoint Slide

Cocrystals of cyt c and b-sclx8 were grown by sitting drop vapor diffusion using a sparse matrix screen (Jena JCSG++ HTS). (14) Small crystals (<40 μm dimension) appeared in eight conditions of the screen. In addition to crystals, a brown precipitate formed at 2–4 equiv of b-sclx8 (Supporting Information, Figure S1). The crystallization conditions contained 20% PEG 3350 or 30% PEG 2000 and 100–200 mM salts including potassium formate, magnesium formate, ammonium formate, or ammonium chloride. Crystals were reproduced manually in similar conditions. b-sclx8 was necessary for crystallization as crystals did not grow in the absence of the macrocycle. Diffraction data were collected at SOLEIL synchrotron to 3.0 Å resolution. Several crystals were tested on two occasions, with no further improvement in resolution. The crystal structure was solved by molecular replacement in space group C121, with four cyt c molecules in the asymmetric unit (Table S1). The presence of b-sclx8 was evident in the unbiased electron density maps (Figure S2), and a stack of three b-sclx8 was modeled. A tube of electron density running through the center of the calixarene stack was modeled as PEG (vide infra), resulting from the use of PEG as the precipitant.

In the crystal structure (PDB entry 7BBT), the b-sclx8 molecules adopt the fully extended, pleated loop conformation. The trimeric stack is ∼6.6 kDa (approximately half the mass of cyt c), ∼2.1 nm long and held together via CH−π and π–π interactions (Figure 3). In the central calixarene, the methylene bridges form CH−π bonds alternately to phenyl rings above or below in the stack. The benzyl-sulfonato arms project outward from the stack for the outer calixarenes, and point up/down for alternate substituents in the central calixarene. As a consequence of the stacking and the projections of the extended arms, the b-sclx8 trimer presents four hydrophobic grooves. Each groove accommodates the N-terminal α-helix of one cyt c by binding the methyl substituents of Thr8 and Thr12 (Figure 3). The slotting of the α-helix into the b-sclx8 groove is complemented by characteristic protein–calixarene charge–charge interactions. The side chain of Thr8 is flanked by Lys4, Lys5, and Lys11 each of which interacts with a sulfonate ion. The Thr12 side chain is flanked by Lys11 and Arg13, the latter forms a cation−π bond to b-sclx8. Thus, in contrast to sclx8, (14,16,18,20) the conformation of b-sclx8 was not altered to “fit” the protein surface, and encapsulation was not achieved. Nevertheless, the trimeric stack presents a binding patch with a hydrophobic core, and a charged periphery that complements the oppositely charged protein surface. A comparison of the NMR data (Figure 2) and the crystal structure (Figure 3) indicates similarities and differences. For example, the NMR suggests binding at Lys4 and Lys5 but not at Arg13.

Figure 3

Figure 3. (A) The N-terminal α-helix of cyt c inserts into a hydrophobic groove presented by a trimeric stack of b-sclx8. The stack is threaded by PEG (navy) giving rise to pseudorotaxane. The 2Fo-Fc electron density map (contoured at 0.5σ) is shown as a blue mesh. (B) Lys4 and Lys5 interact with the calixarene stack via salt bridges to the sulfonate ions. (C) Crystal packing in the cyt c and b-sclx8 structure. Adjacent pairs of b-sclx8 stacks are in close proximity (<6 Å). Axes denote the unit cells.

High Resolution Image
Download MS PowerPoint Slide

Surprisingly, the crystal structure included a PEG fragment of 29 monomers (1.3 kDa) threaded through the cavity of the trimeric b-sclx8 stack, resulting in a [4]pseudorotaxane (Figures 3 and S3). The polyether chain forms multiple van der Waals contacts with all 24 of the phenolic hydroxyls. In addition to threading the cavity, the PEG is laced via CH−π bonds around the benzyl arms projecting away from either end of the stack. There are several examples of calixarene-based pseudorotaxanes reported in the literature, including one with PEG. (22,23,25,26)

Simultaneous interaction of the stacked b-sclx8 with cyt c and PEG resulted in a multicomponent pseudorotaxane–protein assembly (Figure 3). Evidently, intermolecular CH−π and π–π stacking interactions between b-sclx8 were favored over calixarene–protein interactions and induced the formation of the calixarene stack. Similar calixarene–calixarene interactions led to a calix[6]arene dimer in a complex with cyt c, (11) and a calix[8]arene dimer in complex with a lectin. (20) Steric hindrance by the bulky extended arms may have reduced the flexibility of b-sclx8 and decreased the capacity for calixarene molding to the protein surface. The stacking of b-sclx8 resulted in a new type of protein recognition, whereby the trimeric stack presents hydrophobic grooves that can bind an α-helix. Previously, helix mimetics (including foldamers) have been used to slot into helix-accommodating grooves on the protein surface. (1,28) Here, the calixarene stack presents the groove to accommodate the protein.

In parallel to protein recognition, the b-sclx8 stack facilitated pseudorotaxane formation via PEG threading, adding to the collection of calix[8]arene-based rotaxanes reported previously. (22,23) The combination of synthetic machines (rotaxanes) and biological machines (proteins) is an innovative, but underdeveloped topic. In the first reported protein–rotaxane conjugate, a [2]rotaxane was generated via covalent linkage of a pseudorotaxane to cyt c. (29) Previously, we reported crystal structures in which small PEG fragments were trapped by calix[4]arene or calix[8]arene. (10,15,16) The pseudorotaxane of b-sclx8 and PEG reported here raises the possibility of new assembly strategies with PEGylated therapeutics.

Finally, the α-helix binding capacity of b-sclx8 mediated the construction of a novel biohybrid material. The structure is comparable to a recently reported foldamer-cyt c assembly, in which the protein was bound to cylindrical foldamer stacks, of similar size and shape to the pseudorotaxane. (30) Comparison can be made also to protein–cucurbituril cluster assemblies with high macrocycle/protein mass ratios. (7) These biohybrid materials are of interest in crystal engineering, with scope for the inclusion of another biomolecule (protein or peptide) in the assembly. Further research is necessary to investigate the possibilities arising from this novel biohybrid assembly, in particular, the α-helix recognition capacity of the trimeric b-sclx8 stack.

Supporting Information

ARTICLE SECTIONS
Jump To

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.cgd.0c01717.

  • Experimental details, electron density maps and X-ray data collection, processing, and refinement statistics (PDF)

Terms & Conditions

Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

Author Information

ARTICLE SECTIONS
Jump To
  • Corresponding Author
  • Authors
    • Niamh M. Mockler - School of Chemistry, National University of Ireland Galway, University Road, Galway, H91 TK33, Ireland
    • Kiefer O. Ramberg - School of Chemistry, National University of Ireland Galway, University Road, Galway, H91 TK33, Ireland
    • Francesca Guagnini - School of Chemistry, National University of Ireland Galway, University Road, Galway, H91 TK33, Ireland
    • Colin L. Raston - Flinders Institute for Nanoscale Science and Technology, College of Science and Engineering, Flinders University, Bedford Park, South 5042, Australia;  Orcidhttp://orcid.org/0000-0003-4753-0079
  • Notes
    The authors declare no competing financial interest.

Acknowledgments

ARTICLE SECTIONS
Jump To

This research was supported by NUI Galway (College of Science and Engineering postgraduate scholarship to NMM), Royal Society of Chemistry (undergraduate bursary to NMM), NUI (travelling studentship to KOR), Irish Research Council (postdoctoral fellowship GOIPD/2019/513 to F.G.), the Australian Research Council (Discovery grant DP1092810 to C.L.R.) and Science Foundation Ireland (Grants 13/CDA/2168 and 12/RC/2275_P2 to P.B.C.). We thank SOLEIL synchrotron for beam time allocation and the staff at beamline PROXIMA-2A for their assistance. We thank R. Doohan for assistance with NMR spectroscopy.

References

ARTICLE SECTIONS
Jump To

This article references 30 other publications.

  1. 1
    Wells, J. A.; McClendon, C. L. Reaching for high-hanging fruit in drug discovery at protein–protein interfaces. Nature 2007, 450, 1001– 1009,  DOI: 10.1038/nature06526
    [Crossref], [PubMed], [CAS], Google Scholar
    1
    Reaching for high-hanging fruit in drug discovery at protein-protein interfaces
    Wells, James A.; McClendon, Christopher L.
    Nature (London, United Kingdom) (2007), 450 (7172), 1001-1009CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)
    A review. Targeting the interfaces between proteins has huge therapeutic potential, but discovering small-mol. drugs that disrupt protein-protein interactions is an enormous challenge. Several recent success stories, however, indicate that protein-protein interfaces might be more tractable than has been thought. These studies discovered small mols. that bind with drug-like potencies to 'hotspots' on the contact surfaces involved in protein-protein interactions. Remarkably, these small mols. bind deeper within the contact surface of the target protein, and bind with much higher efficiencies, than do the contact atoms of the natural protein partner. Some of these small mols. are now making their way through clin. trials, so this high-hanging fruit might not be far out of reach.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXhsVaqtr7F&md5=e7ed69fd8c362a71c4b99f029c16a6fc
  2. 2
    Luo, Q.; Hou, C.; Bai, Y.; Wang, R.; Liu, J. Protein assembly: versatile approaches to construct highly ordered nanostructures. Chem. Rev. 2016, 116, 13571– 13632,  DOI: 10.1021/acs.chemrev.6b00228
    [ACS Full Text ACS Full Text], [CAS], Google Scholar
    2
    Protein Assembly: Versatile Approaches to Construct Highly Ordered Nanostructures
    Luo, Quan; Hou, Chunxi; Bai, Yushi; Wang, Ruibing; Liu, Junqiu
    Chemical Reviews (Washington, DC, United States) (2016), 116 (22), 13571-13632CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)
    A review. Nature endows life with a wide variety of sophisticated, synergistic and highly functional protein assemblies. Following Nature's inspiration to assemble protein building blocks into exquisite nanostructures is emerging as a fascinating research field. Dictating protein assembly to obtain highly ordered nanostructures and sophisticated functions not only provides a powerful tool to understand the natural protein assembly process, but also offers access to advanced biomaterials. Over the past couple of decades, the field of protein assembly has undergone unexpected and rapid developments, and various innovative strategies have been proposed. This review outlines recent advances in the field of protein assembly and summarizes several strategies, including biotechnol. strategies, chem. strategies, and combinations of these approaches, for manipulating proteins to self-assemble into desired nanostructures. The emergent applications of protein assemblies as versatile platforms to design a wide variety of attractive functional materials with improved performances have also been discussed. The goal of this review is to highlight the importance of this highly interdisciplinary field and to promote its growth in a diverse variety of research fields ranging from nanoscience and material science to synthetic biol.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhsVeksbnO&md5=0802f364ddc303d7f32253d17af670f0
  3. 3
    van Dun, S.; Ottmann, C.; Milroy, L.-G.; Brunsveld, L. Supramolecular chemistry targeting proteins. J. Am. Chem. Soc. 2017, 139, 13960– 13968,  DOI: 10.1021/jacs.7b01979
    [ACS Full Text ACS Full Text], [CAS], Google Scholar
    3
    Supramolecular Chemistry Targeting Proteins
    van Dun, Sam; Ottmann, Christian; Milroy, Lech-Gustav; Brunsveld, Luc
    Journal of the American Chemical Society (2017), 139 (40), 13960-13968CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
    A review. The specific recognition of protein surface elements is a fundamental challenge in the life sciences. New developments in this field will form the basis of advanced therapeutic approaches and lead to applications such as sensors, affinity tags, immobilization techniques, and protein-based materials. Synthetic supramol. mols. and materials are creating new opportunities for protein recognition that are orthogonal to classical small mol. and protein-based approaches. As outlined here, their unique mol. features enable the recognition of amino acids, peptides, and even whole protein surfaces, which can be applied to the modulation and assembly of proteins. The authors believe that structural insights into these processes are of great value for the further development of this field and have therefore focused this Perspective on contributions that provide such structural data.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhsFeit7vL&md5=56422173d029b081e10d773705b8a478
  4. 4
    Supramolecular Protein Chemistry: Assembly, Architecture and Application; Crowley, P. B., Ed.; Royal Society of Chemistry: Cambridge, 2020; pp 1– 312.
    [Crossref], Google Scholar
    There is no corresponding record for this reference.
  5. 5
    Webber, M. J.; Appel, E. A.; Vinciguerra, B.; Cortinas, A. B.; Thapa, L. S.; Jhunjhunwala, S.; Isaacs, L.; Langer, R.; Anderson, D. G. Supramolecular PEGylation of biopharmaceuticals. Proc. Natl. Acad. Sci. U. S. A. 2016, 113, 14189– 14194,  DOI: 10.1073/pnas.1616639113
    [Crossref], [PubMed], [CAS], Google Scholar
    5
    Supramolecular PEGylation of biopharmaceuticals
    Webber, Matthew J.; Appel, Eric A.; Vinciguerra, Brittany; Cortinas, Abel B.; Thapa, Lavanya S.; Jhunjhunwala, Siddharth; Isaacs, Lyle; Langer, Robert; Anderson, Daniel G.
    Proceedings of the National Academy of Sciences of the United States of America (2016), 113 (50), 14189-14194CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)
    The covalent modification of therapeutic biomols. has been broadly explored, leading to a no. of clin. approved modified protein drugs. These modifications are typically intended to address challenges arising in biopharmaceutical practice by promoting improved stability and shelf life of therapeutic proteins in formulation, or modifying pharmacokinetics in the body. Toward these objectives, covalent modification with poly(ethylene glycol) (PEG) has been a common direction. Here, a platform approach to biopharmaceutical modification is described that relies on noncovalent, supramol. host-guest interactions to endow proteins with prosthetic functionality. Specifically, a series of cucurbit[7]uril (CB[7])-PEG conjugates are shown to substantially increase the stability of three distinct protein drugs in formulation. Leveraging the known and high-affinity interaction between CB[7] and an N-terminal arom. residue on one specific protein drug, insulin, further results in altering of its pharmacol. properties in vivo by extending activity in a manner dependent on mol. wt. of the attached PEG chain. Supramol. modification of therapeutic proteins affords a noncovalent route to modify its properties, improving protein stability and activity as a formulation excipient. Furthermore, this offers a modular approach to append functionality to biopharmaceuticals by noncovalent modification with other mols. or polymers, for applications in formulation or therapy.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhvFCnsL%252FN&md5=4a518f1dec10cd5c78c7cbb6e74149db
  6. 6
    de Vink, P. J.; Briels, J. M.; Schrader, T.; Milroy, L.-G.; Brunsveld, L.; Ottmann, C. A binary bivalent supramolecular assembly platform based on cucurbit[8]uril and dimeric adapter protein 14–3-3. Angew. Chem., Int. Ed. 2017, 56, 8998– 9002,  DOI: 10.1002/anie.201701807
    [Crossref], [CAS], Google Scholar
    6
    A binary bivalent supramolecular assembly platform based on cucurbit[8]uril and dimeric adapter protein 14-3-3
    de Vink, Pim J.; Briels, Jeroen M.; Schrader, Thomas; Milroy, Lech-Gustav; Brunsveld, Luc; Ottmann, Christian
    Angewandte Chemie, International Edition (2017), 56 (31), 8998-9002CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
    Interactions between proteins frequently involve recognition sequences based on multivalent binding events. Dimeric 14-3-3 adapter proteins are a prominent example and typically bind partner proteins in a phosphorylation-dependent monovalent or bivalent manner. Here, we describe the development of a cucurbit[8]uril (Q8)-based supramol. system, which in conjunction with the 14-3-3β protein dimer acts as a binary and bivalent protein assembly platform. We fused the Phe-Gly-Gly (FGG) tripeptide motif to the N-terminus of the 14-3-3-binding epitope of the estrogen receptor α (ERα) for selective binding to Q8. Q8-induced dimerization of the ERα epitope augmented its affinity towards 14-3-3β through a binary bivalent binding mode. The crystal structure of the Q8-induced ternary complex revealed mol. insight into the multiple supramol. interactions between the protein, the peptide, and Q8.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhtV2gs7%252FO&md5=0450a9a632f031e42a7db38c7e9d900d
  7. 7
    Guagnini, F.; Engilberge, S.; Ramberg, K. O.; Pérez, J.; Crowley, P. B. Engineered assembly of a protein-cucurbituril biohybrid. Chem. Commun. 2020, 56, 360– 363,  DOI: 10.1039/C9CC07198A
    [Crossref], [PubMed], [CAS], Google Scholar
    7
    Engineered assembly of a protein-cucurbituril biohybrid
    Guagnini, Francesca; Engilberge, Sylvain; Ramberg, Kiefer O.; Perez, Javier; Crowley, Peter B.
    Chemical Communications (Cambridge, United Kingdom) (2020), 56 (3), 360-363CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
    A cryst. biohybrid with a 4 : 1 protein : cucurbituril mass ratio is presented. This result was achieved by engineering addnl. cucurbit[7]uril (Q7) binding sites into a β-propeller protein. In contrast to the parent protein, Q7-controlled assembly of the engineered variant occurred in soln., as evidenced by NMR and SAXS measurements.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXitlWhsb%252FL&md5=7816ef6488835461ce1aa36c24f0ca4f
  8. 8
    Guagnini, F.; Engilberge, S.; Flood, R. J.; Ramberg, K. O.; Crowley, P. B. Metal-mediated protein–cucurbituril crystalline architectures. Cryst. Growth Des. 2020, 20, 6983– 6989,  DOI: 10.1021/acs.cgd.0c01023
    [ACS Full Text ACS Full Text], [CAS], Google Scholar
    8
    Metal-Mediated Protein-Cucurbituril Crystalline Architectures
    Guagnini, Francesca; Engilberge, Sylvain; Flood, Ronan J.; Ramberg, Kiefer O.; Crowley, Peter B.
    Crystal Growth & Design (2020), 20 (10), 6983-6989CODEN: CGDEFU; ISSN:1528-7483. (American Chemical Society)
    Controlled protein assembly is an enabling technol., for example, in the bottom-up fabrication of biomaterials. This paper describes the assembly of a β-propeller protein using two orthogonal interaction modes. Previously, protein assembly was directed by metal coordination or macrocycle complexation. Here, the authors demonstrate the combination of metal coordination and macrocycle complexation for controlled assembly. An established protein-cucurbit[7]uril (Q7) assembly, which relies on trimeric Q7 clusters, was modified by the inclusion of metal-binding sites in the protein. The application of zinc-histidine coordination to tune the Q7-induced assembly resulted in metallo-bioorg. cryst. architectures. The relative arrangement of the protein-Q7 layers was reorganized by the zinc bridging ions. One structure resulted in a different type of protein-Q7 packing that involves Q7 dimers. Apparently, Q7 is a versatile mol. glue that can be combined with metal-mediated protein assembly. This dual strategy expands significantly the toolkit for engineered assembly. A protein-cucurbit[7]uril (Q7) assembly was engineered by the inclusion of zinc-binding sites to yield distinct arrangements of protein-Q7 layers.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhs1KiurzL&md5=e873ee78efefe7d20a31182cdfca1fc0
  9. 9
    McGovern, R. E.; Fernandes, H.; Khan, A. R.; Power, N. P.; Crowley, P. B. Protein camouflage in cytochrome c-calixarene complexes. Nat. Chem. 2012, 4, 527– 533,  DOI: 10.1038/nchem.1342
    [Crossref], [PubMed], [CAS], Google Scholar
    9
    Protein camouflage in cytochrome c-calixarene complexes
    McGovern, Roise E.; Fernandes, Humberto; Khan, Amir R.; Power, Nicholas P.; Crowley, Peter B.
    Nature Chemistry (2012), 4 (7), 527-533CODEN: NCAHBB; ISSN:1755-4330. (Nature Publishing Group)
    Small mols. that recognize protein surfaces are important tools for modifying protein interaction properties. Since the 1980s, several thousand studies concerning calixarenes and host-guest interactions have been published. Although there is growing interest in protein-calixarene interactions, only limited structural information has been available to date. We now report the crystal structure of a protein-calixarene complex. The water-sol. p-sulfonatocalix[4]arene is shown to bind the lysine-rich cytochrome c at three different sites. Binding curves obtained from NMR titrns. reveal an interaction process that involves two or more binding sites. Together, the data indicate a dynamic complex in which the calixarene explores the surface of cytochrome c. In addn. to providing valuable information on protein recognition, the data also indicate that the calixarene is a mediator of protein-protein interactions, with potential applications in generating assemblies and promoting crystn.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xmt1Gqt7Y%253D&md5=36831f24c65387bd400e7e1e5de177b1
  10. 10
    McGovern, R. E.; McCarthy, A. A.; Crowley, P. B. Protein assembly mediated by sulfonatocalix[4]arene. Chem. Commun. 2014, 50, 10412– 10415,  DOI: 10.1039/C4CC04897K
    [Crossref], [PubMed], [CAS], Google Scholar
    10
    Protein assembly mediated by sulfonatocalix[4]arene
    McGovern, Roise E.; McCarthy, Andrew A.; Crowley, Peter B.
    Chemical Communications (Cambridge, United Kingdom) (2014), 50 (72), 10412-10415CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
    A crystal structure of lysozyme in complex with p-sulfonato-calix[4]arene (sclx4) reveals a linear assembly of protein tetramers glued together by protein-calixarene interactions. One interaction involves encapsulation of the highly exposed C-terminal Arg128. The other involves an intricate protein-bound complex of sclx4, Mg2+ and a fragment of polyethylene glycol.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtF2ksLjF&md5=5c8a69a3208c78f9c8e91bd8ad13ba81
  11. 11
    Rennie, M. L.; Doolan, A. M.; Raston, C. L.; Crowley, P. B. Protein dimerization on a phosphonated calix[6]arene disc. Angew. Chem., Int. Ed. 2017, 56, 5517– 5521,  DOI: 10.1002/anie.201701500
    [Crossref], [CAS], Google Scholar
    11
    Protein dimerization on a phosphonated calix[6]arene disc
    Rennie, Martin L.; Doolan, Aishling M.; Raston, Colin L.; Crowley, Peter B.
    Angewandte Chemie, International Edition (2017), 56 (20), 5517-5521CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
    Complex formation between cationic cytochrome c and the water-sol., poly-anionic p-phosphonatocalix[6]arene (pclx6) was investigated. A crystal structure (at 1.8 Å resoln.) revealed a remarkable dimeric disk of pclx6 that acts like glue to mediate a sym. (C2) protein dimer. The calixarene disk had a diam. of ∼1.5 nm and masked ∼360 Å2 of the protein surface. The key protein-calixarene contacts occurred via 2 linchpin Lys residues, with addnl. contacts provided by a small hydrophobic patch. The protein-calixarene supramol. assemblies were obsd. in soln. by size-exclusion chromatog. with multi-angle light scattering and NMR spectroscopy. Using isothermal titrn. calorimetry and NMR data, an apparent Kd in the low micromolar range was detd. for the charge-rich protein-calixarene complex. In contrast to p-sulfonatocalix[4]arene, the larger pclx6 had a single, well-defined binding site that mediated the assembly of cytochrome c in soln.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXmtVyhurs%253D&md5=68aaa93576986b1a0eacfd07838c7ddc
  12. 12
    Doolan, A. M.; Rennie, M. L.; Crowley, P. B. Protein recognition by functionalized sulfonato-calix[4]arenes. Chem. - Eur. J. 2018, 24, 984– 991,  DOI: 10.1002/chem.201704931
    [Crossref], [PubMed], [CAS], Google Scholar
    12
    Protein recognition by functionalized sulfonatocalix[4]arenes
    Doolan, Aishling M.; Rennie, Martin L.; Crowley, Peter B.
    Chemistry - A European Journal (2018), 24 (4), 984-991CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)
    The interactions of 2 mono-functionalized sulfonatocalix[4]arenes with cytochrome c were investigated by structural and thermodn. methods. The replacement of a single sulfonate with either a bromo or a Ph substituent resulted in altered recognition of cytochrome c as evidenced by x-ray crystallog. The bromo-substituted ligand yielded a new binding mode in which a self-encapsulated calixarene dimer contributed to crystal packing. This ligand also formed a weak halogen bond with the protein. The phenyl-substituted ligand was bound to Lys-4 of cytochrome c, in a 1.7 Å-resoln. crystal structure. A dimeric packing arrangement mediated by ligand-ligand contacts in the crystal suggested a possible assembly mechanism. The different protein recognition properties of these calixarenes were discussed.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhvFyjs7jM&md5=14cd0dccf75aabe744b6d9c4bfb0faab
  13. 13
    Alex, J. M.; Rennie, M. L.; Volpi, S.; Sansone, F.; Casnati, A.; Crowley, P. B. Phosphonated calixarene as a “molecular glue” for protein crystallization. Cryst. Growth Des. 2018, 18, 2467– 2473,  DOI: 10.1021/acs.cgd.8b00092
    [ACS Full Text ACS Full Text], [CAS], Google Scholar
    13
    Phosphonated Calixarene as a "Molecular Glue" for Protein Crystallization
    Alex, Jimi M.; Rennie, Martin L.; Volpi, Stefano; Sansone, Francesco; Casnati, Alessandro; Crowley, Peter B.
    Crystal Growth & Design (2018), 18 (4), 2467-2473CODEN: CGDEFU; ISSN:1528-7483. (American Chemical Society)
    Protein crystn. remains a serious bottleneck to structure detn. by X-ray diffraction methods. Compds. acting as "mol. glue" provide a promising strategy to overcome this bottleneck. Such mols. interact via noncovalent bonds with two or more protein surfaces to promote lattice formation. Here, we report a 1.5 Å resoln. crystal structure of lysine-rich cytochrome c complexed with p-phosphonatomethyl-calix[4]arene (pmclx4). Evidence for complex formation in soln. was provided by NMR studies. Similar to p-sulfonato-calix[4]arene (sclx4), the cavity of pmclx4 entrapped a single lysine side chain. Interesting features of protein recognition by the phosphonate substituents were identified in the crystal structure. A new calixarene binding site was identified at Lys54. The electron d. at this site indicated two distinct calixarene conformers, suggesting a degree of ligand mobility. The role of pmclx4 in protein crystal packing (mol. glue and patchy particle model) as well as differences in protein-binding with respect to sclx4 are discussed.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXks1yiu7c%253D&md5=5cc8b55005f39d13b646bb0ecaf55182
  14. 14
    Rennie, M. L.; Fox, G. C.; Pérez, J.; Crowley, P. B. Auto-regulated protein assembly on a supramolecular scaffold. Angew. Chem., Int. Ed. 2018, 57, 13764– 13769,  DOI: 10.1002/anie.201807490
    [Crossref], [CAS], Google Scholar
    14
    Auto-regulated Protein Assembly on a Supramolecular Scaffold
    Rennie, Martin L.; Fox, Gavin C.; Perez, Javier; Crowley, Peter B.
    Angewandte Chemie, International Edition (2018), 57 (42), 13764-13769CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
    Controlled protein assembly provides a means to regulate function. Supramol. building blocks, including rigid macrocycles, are versatile triggers of protein assembly. Now it is shown that sulfonato-calix[8]arene (sclx8) mediates the formation of cytochrome c tetramers in soln. This tetramer spontaneously disassembles at ≥2 equiv of sclx8, providing a remarkable example of auto-regulation. Using X-ray crystallog. the sclx8 binding sites on cytochrome c were characterized. Crystal structures at different protein-ligand ratios reveal varying degrees (up to 35 %) of protein surface coverage by the flexible calixarene and suggest a mechanism for oligomer disassembly. The soln. structure of the oligomer was characterized by small-angle X-ray scattering. Overall, the data indicate calixarene-controlled protein assembly and disassembly without the requirement for a competitive inhibitor, and point to protein encapsulation by a flexible macrocycle.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhslWjurjE&md5=479efd470dec2b3bf8798c0218ab7613
  15. 15
    Mummidivarapu, V. V. S.; Rennie, M. L.; Doolan, A. M.; Crowley, P. B. Noncovalent PEGylation via sulfonatocalix[4]arene - A crystallographic proof. Bioconjugate Chem. 2018, 29, 3999– 4003,  DOI: 10.1021/acs.bioconjchem.8b00769
    [ACS Full Text ACS Full Text], [CAS], Google Scholar
    15
    Noncovalent PEGylation via sulfonatocalix[4]arene - A crystallographic proof
    Mummidivarapu, V. V. Sreenivasu; Rennie, Martin L.; Doolan, Aishling M.; Crowley, Peter B.
    Bioconjugate Chemistry (2018), 29 (12), 3999-4003CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
    Noncovalent or supramol. PEGylation, in combination with the site of administration, has great potential to increase the half-life of therapeutic proteins. To date, a variety of noncovalent PEGylation strategies have been devised. However, questions remain concerning the nature of the protein-poly(ethylene glycol) (PEG) interaction. Here, we report structural analyses of a model system that comprised Lys-rich cytochrome c and 2 PEGylated variants of sulfonatocalix[4]arene. Complex formation was characterized in soln. by NMR spectroscopy. It was found that mono- or di-PEGylated sulfonatocalix[4]arene bound the protein similar to the parent calixarene. X-ray crystal structures at <2.7 Å resoln. of the PEGylated derivs. in complex with cytochrome c revealed that the PEG chains were mostly disordered or encapsulated within the calixarene cavity. These results suggest that there was minimal interaction between the PEG and the protein surface, providing further evidence in favor of PEG maintaining a random coil conformation.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXit1Wmur7J&md5=5b579dea529386fb7f433bd6e4f59bbb
  16. 16
    Alex, J. M.; Rennie, M. L.; Engilberge, S.; Lehoczki, G.; Dorottya, H.; Fizil, A.; Batta, G.; Crowley, P. B. Calixarene-mediated assembly of a small antifungal protein. IUCrJ 2019, 6, 238– 247,  DOI: 10.1107/S2052252519000411
    [Crossref], [PubMed], [CAS], Google Scholar
    16
    Calixarene-mediated assembly of a small antifungal protein
    Alex, Jimi M.; Rennie, Martin L.; Engilberge, Sylvain; Lehoczki, Gabor; Dorottya, Hajdu; Fizil, Adam; Batta, Gyula; Crowley, Peter B.
    IUCrJ (2019), 6 (2), 238-247CODEN: IUCRAJ; ISSN:2052-2525. (International Union of Crystallography)
    Synthetic macrocycles such as calixarenes and cucurbiturils are increasingly applied as mediators of protein assembly and crystn. The macrocycle can facilitate assembly by providing a surface on which two or more proteins bind simultaneously. This work explores the capacity of the sulfonato-calix[n]arene (sclxn) series to effect crystn. of PAF, a small, cationic antifungal protein. Co-crystn. with sclx4, sclx6 or sclx8 led to high-resoln. crystal structures. In the absence of sclxn, diffraction-quality crystals of PAF were not obtained. Interestingly, all three sclxn were bound to a similar patch on PAF. The largest and most flexible variant, sclx8, yielded a dimer of PAF. Complex formation was evident in soln. via NMR and ITC expts., showing more pronounced effects with increasing macrocycle size. In agreement with the crystal structure, the ITC data suggested that sclx8 acts as a bidentate ligand. The contributions of calixarene size/conformation to protein recognition and assembly are discussed. Finally, it is suggested that the conserved binding site for anionic calixarenes implicates this region of PAF in membrane binding, which is a prerequisite for antifungal activity.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXksVajtr8%253D&md5=71ee504263ead42d06de3c8a11d1fd44
  17. 17
    Engilberge, S.; Rennie, M. L.; Crowley, P. B. Calixarene Capture of Partially Unfolded Cytochrome c. FEBS Lett. 2019, 593, 2112– 2117,  DOI: 10.1002/1873-3468.13512
    [Crossref], [PubMed], [CAS], Google Scholar
    17
    Calixarene capture of partially unfolded cytochrome c
    Engilberge, Sylvain; Rennie, Martin L.; Crowley, Peter B.
    FEBS Letters (2019), 593 (16), 2112-2117CODEN: FEBLAL; ISSN:0014-5793. (Wiley-Blackwell)
    Supramol. receptors such as water-sol. calixarenes are in development as 'mol. glues' for protein assembly. Here, we obtained cocrystals of sulfonato-calix[6]arene (sclx6) and yeast cytochrome c (cytc) in the presence of imidazole. A crystal structure at 2.65 Å resoln. reveals major structural rearrangement and disorder in imidazole-bound cytc. The largest protein-calixarene interface involves 440 Å2 of the protein surface with key contacts at Arg13, Lys73, and Lys79. These lysines participate in alk. transitions of cytc and are part of Ω-loop D, which is substantially restructured in the complex with sclx6. The structural modification also includes Ω-loop C, which is disordered (residues 41-55 inclusive). These results suggest the possibility of using supramol. scaffolds to trap partially disordered proteins.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhtlamu7nI&md5=7b9cc49d6ba9396737a32787e49c5727
  18. 18
    Engilberge, S.; Rennie, M. L.; Dumont, E.; Crowley, P. B. Tuning protein frameworks via auxiliary supramolecular interactions. ACS Nano 2019, 13, 10343– 10350,  DOI: 10.1021/acsnano.9b04115
    [ACS Full Text ACS Full Text], [CAS], Google Scholar
    18
    Tuning Protein Frameworks via Auxiliary Supramolecular Interactions
    Engilberge, Sylvain; Rennie, Martin L.; Dumont, Elise; Crowley, Peter B.
    ACS Nano (2019), 13 (9), 10343-10350CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)
    Protein crystals with their precise, periodic array of functional building blocks have potential applications in biomaterials, sensing, and catalysis. This paper describes how a highly porous cryst. framework of a cationic redox protein and an anionic macrocycle can be modulated by a small cationic effector. Ternary composites of protein (∼13 kDa), calix[8]arene (∼1.5 kDa), and effector (∼0.2 kDa) formed distinct cryst. architectures, dependent on the effector concn. and the crystn. technique. A combination of X-ray crystallog. and d. functional theory (DFT) calcns. was used to decipher the framework variations, which appear to be dependent on a calixarene conformation change mediated by the effector. This "switch" calixarene was obsd. in three states, each of which is assocd. with a different interaction network. Two structures obtained by co-crystn. with the effector contained an addnl. protein "pillar", resulting in framework duplication and decreased porosity. These results suggest how protein assembly can be engineered by supramol. host-guest interactions.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhslegtLzM&md5=7c36109bdf1fe9d43d633c25320a98e4
  19. 19
    Alex, J. M.; Brancatelli, G.; Volpi, S.; Bonaccorso, C.; Casnati, A.; Geremia, S.; Crowley, P. B. Probing the determinants of porosity in protein frameworks: co-crystals of cytochrome c and an octaanionic calix[4]arene. Org. Biomol. Chem. 2020, 18, 211– 214,  DOI: 10.1039/C9OB02275A
    [Crossref], [PubMed], [CAS], Google Scholar
    19
    Probing the determinants of porosity in protein frameworks: co-crystals of cytochrome c and an octa-anionic calix[4]arene
    Alex, Jimi M.; Brancatelli, Giovanna; Volpi, Stefano; Bonaccorso, Carmela; Casnati, Alessandro; Geremia, Silvano; Crowley, Peter B.
    Organic & Biomolecular Chemistry (2020), 18 (2), 211-214CODEN: OBCRAK; ISSN:1477-0520. (Royal Society of Chemistry)
    Sulfonato-calix[n]arenes (sclxn) are promising tools to generate cryst. protein frameworks. We report, for the first time, a lower rim functionalized octa-anionic calix[4]arene (sclx4mc) in complex with proteins. Two crystal structures of sclx4mc bound to yeast or horse heart cytochrome c (cytc) are described. Highly porous honeycomb or tubular assemblies were obtained with yeast or horse cytc, resp. Related frameworks were obtained previously with sclx8 and sclx6 but not with sclx4, suggesting that the ligand charge is a detg. factor.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXitlWhsLfN&md5=e964ed7e524cc096bf51d8152b62cc73
  20. 20
    Ramberg, K. O.; Engilberge, S.; Skorek, T.; Crowley, P. B. Facile fabrication of protein-macrocycle frameworks. J. Am. Chem. Soc. 2021,  DOI: 10.1021/jacs.0c10697
    [ACS Full Text ACS Full Text], Google Scholar
    There is no corresponding record for this reference.
  21. 21
    Abascal, N. C.; Regan, L. The past, present and future of protein-based materials. Open Biol. 2018, 8, 180113,  DOI: 10.1098/rsob.180113
    [Crossref], [PubMed], [CAS], Google Scholar
    21
    The past, present and future of protein-based materials
    Abascal, Nadia C.; Regan, Lynne
    Open Biology (2018), 8 (10), 180113CODEN: OBPICQ; ISSN:2046-2441. (Royal Society)
    A review. Protein-based materials are finding new uses and applications after millennia of impacting the daily life of humans. Some of the earliest uses of protein-based materials are still evident in silk and wool textiles and leather goods. Today, even as silks, wools and leathers are still be used in traditional ways, these proteins are now seen as promising materials for biomaterials, vehicles of drug delivery and components of high-tech fabrics. With the advent of biosynthetic methods and streamlined means of protein purifn., protein-based materials-recombinant and otherwise-are being used in a host of applications at the cutting edge of medicine, electronics, materials science and even fashion. This commentary aims to discuss a handful of these applications while taking a crit. look at where protein-based materials may be used in the future.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXpsFelsbs%253D&md5=939fe952bdff35b894425d2a9dab0817
  22. 22
    Yamagishi, T.-A.; Kawahara, A.; Kita, J.; Hoshima, M.; Umehara, A.; Ishida, S.-I.; Nakamoto, Y. In situ polycondensation of p-tert-butylphenol in the presence of poly(ethylene glycol)s for preparation of polyrotaxanes. Macromolecules 2001, 34, 6565– 6570,  DOI: 10.1021/ma010033e
    [ACS Full Text ACS Full Text], [CAS], Google Scholar
    22
    In Situ Polycondensation of p-tert-Butylphenol in the Presence of Poly(ethylene glycol)s for Preparation of Polyrotaxanes
    Yamagishi, Tada-Aki; Kawahara, Akihiko; Kita, Junko; Hoshima, Miho; Umehara, Ayako; Ishida, Shin-ichiro; Nakamoto, Yoshiaki
    Macromolecules (2001), 34 (19), 6565-6570CODEN: MAMOBX; ISSN:0024-9297. (American Chemical Society)
    A new polyrotaxane was formed by the polycondensation of p-tert-butylphenol (BP) with paraformaldehyde in the presence of poly(ethylene glycol)s, (PEG)s, of various mol. wts. The polyrotaxane of BP oligomers with PEG was obtained when the PEG of av. mol. wts. between 1000 and 10,000 were used in the polycondensation. The polyrotaxane yield and the compn. were dependent on the mol. wt. of PEG. The mol. structure was detd. by FT-IR and 1H NMR spectroscopies and the thermal properties by DSC measurements. 1H NMR spectra of the complexes showed a pair of doublets in the methylene region, which correspond to the methylene protons between phenolic rings in p-tert-butylcalixarenes. The FT-IR spectra and DSC curves were different from those of the blend of linear p-tert-butylphenolic resins with PEG and pure p-tert-butylcalix[8]arene, resp. Calixarenes slipped off the backbone PEG by heating the polyrotaxane in ethylene glycol at 180°. The structure of the dethreaded calixarenes was detd. by 1H NMR, and they were found to be p-tert-butylcalix[8]arenes and a few p-tert-butylcalix[4]arenes. From the characteristic results it was found that the polyrotaxane obtained by the in situ polycondensation of BP was composed of p-tert-butylcalix[8]arenes penetrated by PEG; i.e., this was a calix[8]arene-based polyrotaxane.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3MXlvFamsrg%253D&md5=276a3be2167028332f4ee93016b872c3
  23. 23
    Gaeta, C.; Talotta, C.; Margarucci, L.; Casapullo, A.; Neri, P. Through-the-annulus threading of the larger calix[8]arene macrocycle. J. Org. Chem. 2013, 78, 7627– 7638,  DOI: 10.1021/jo401206j
    [ACS Full Text ACS Full Text], [CAS], Google Scholar
    23
    Through-the-Annulus Threading of the Larger Calix[8]arene Macrocycle
    Gaeta, Carmine; Talotta, Carmen; Margarucci, Luigi; Casapullo, Agostino; Neri, Placido
    Journal of Organic Chemistry (2013), 78 (15), 7627-7638CODEN: JOCEAH; ISSN:0022-3263. (American Chemical Society)
    A complete study of the through-the-annulus threading of the larger calix[8]arene macrocycle with di-n-alkylammonium cations was performed in the presence of the superweak TFPB counterion. Thus, such threading occurs only upon partial preorganization of the calix[8]arene macroring by intramol. bridging. In particular, 1,5-bridged calix[8]arenes with a meta- or para-xylylene bridge (I and II) gave pseudo[2]rotaxanes in which one dialkylammonium axle was threaded into one of the two subcavities of the calix[8]-wheel. Conformational studies by using chem. shift surface maps and DFT calcns. evidenced a 3/4-cone geometry for these subcavities. Higher pseudorotaxane Kass values were obtained for calix[8]-wheels I and II with respect to calix[6]-host III, due to the cooperative effect of their two subcavities. Dynamic NMR studies on calix[8]-pseudorotaxanes evidenced a direct correlation between Kass (and ΔGass) values and energy barriers for calix inversion due to the effectiveness of thread templation. In accordance with DFT calcns., an endo-alkyl preference, over the endo-benzyl one, was obsd. by threading calix[8]-wheel II with the directional n-butylbenzylammonium axle.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtVKqt7jP&md5=bf2eaeb0567f03801437ade7d3c64605
  24. 24
    Stoddart, J. F. Mechanically interlocked molecules (MIMs) – Molecular Shuttles, Switches, and Machines (Nobel Lecture). Angew. Chem., Int. Ed. 2017, 56, 11094– 11125,  DOI: 10.1002/anie.201703216
    [Crossref], [CAS], Google Scholar
    24
    Mechanically Interlocked Molecules (MIMs)-Molecular Shuttles, Switches, and Machines (Nobel Lecture)
    Stoddart, J. Fraser
    Angewandte Chemie, International Edition (2017), 56 (37), 11094-11125CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
    An autobiog. for J. Fraser Stoddart, born May 24, 1942 in Edinburgh, United Kingdom, is presented. Stoddart is a professor of chem. and head of the Stoddart Mechanostereochem. Group at Northwestern University in the United States.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhtlCnsbzI&md5=d5a5e6f75cac3988ee716fb2423bc519
  25. 25
    Gaeta, C.; Talotta, C.; Neri, P. Calix[6]arene-based atropoisomeric pseudo[2]rotaxanes. Beilstein J. Org. Chem. 2018, 14, 2112– 2124,  DOI: 10.3762/bjoc.14.186
    [Crossref], [PubMed], [CAS], Google Scholar
    25
    Calix[6]arene-based atropoisomeric pseudo[2]rotaxanes
    Gaeta, Carmine; Talotta, Carmen; Neri, Placido
    Beilstein Journal of Organic Chemistry (2018), 14 (), 2112-2124CODEN: BJOCBH; ISSN:1860-5397. (Beilstein-Institut zur Foerderung der Chemischen Wissenschaften)
    Some examples of atropisomeric pseudorotaxanes in which the isomerism arises by the different conformations adopted by the wheel are reported here. Upon threading hexahexyloxycalix[6]arene I (R = n-C6H13) with ammonium axles II (R1 = Ph or trifluoromethyl) resp., two atropisomeric pseudorotaxanes were formed in which the calix[6]-wheel I adopts the 1,2,3-alternate and cone conformations. The interconversion between them cannot be obtained by simple rotation around the ArCH2Ar bonds of the calixarene wheel, which is blocked by the presence of the axle inside its cavity. Therefore, it can only be obtained through a mechanism of de-threading/re-threading of the axle. In all the examd. cases, the 1,2,3-alternate and cone atropisomers are, resp., the kinetic and thermodn. ones.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhvFyrt7bK&md5=3bb0951056533a8e564f8c5f75cbbeec
  26. 26
    Orlandini, G.; Casimiro, L.; Bazzoni, M.; Cogliati, B.; Credi, A.; Lucarini, M.; Silvi, S.; Arduini, A.; Secchi, A. Synthesis and properties of a redox-switchable calix[6]arene-based molecular lasso. Org. Chem. Front. 2020, 7, 648– 659,  DOI: 10.1039/C9QO01379B
    [Crossref], [CAS], Google Scholar
    26
    Synthesis and properties of a redox-switchable calix[6]arene-based molecular lasso
    Orlandini, Guido; Casimiro, Lorenzo; Bazzoni, Margherita; Cogliati, Beatrice; Credi, Alberto; Lucarini, Marco; Silvi, Serena; Arduini, Arturo; Secchi, Andrea
    Organic Chemistry Frontiers (2020), 7 (4), 648-659CODEN: OCFRA8; ISSN:2052-4129. (Royal Society of Chemistry)
    The synthesis and characterization of calix[6]arene-based lasso-like mol. structures is described. These interwoven structures consist of an electrochem. responsive N,N'-dialkylviologen arm covalently anchored at the upper rim of a triphenylureido calix[6]arene-based wheel. Upon redn. of the viologen core, a hollow tridimensional macrocyclic structure can be generated. This process is reversible, and the original lasso-like structure can be regenerated by oxidizing the viologen arm to its original dicationic form. Electrochem. and EPR techniques investigated the ability of the system to perform threading/dethreading movements upon redox switching. The functionalization of the arm ω-hydroxy ending with a bulky diphenylacetyl group converts the self-threaded structure in a blocked interwoven mol. compd. belonging to the class of [1]rotaxanes. The ability to form dimeric structures in the shape of a [c2]daisy chain was also demonstrated, an unprecedented result for calixarene macrocycles.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhvF2lsw%253D%253D&md5=6c58706d05589f780d5b3ffab4fa03ae
  27. 27
    Hubble, L. J.; Clark, T. E.; Makha, M.; Raston, C. L. Selective diameter uptake of single-walled carbon nanotubes in water using phosphonated calixarenes and ‘extended arm’ sulfonated calixarenes. J. Mater. Chem. 2008, 18, 5961– 5966,  DOI: 10.1039/b814904f
    [Crossref], [CAS], Google Scholar
    27
    Selective diameter uptake of single-walled carbon nanotubes in water using phosphonated calixarenes and extended arm' sulfonated calixarenes
    Hubble, Lee J.; Clark, Thomas E.; Makha, Mohamed; Raston, Colin L.
    Journal of Materials Chemistry (2008), 18 (48), 5961-5966CODEN: JMACEP; ISSN:0959-9428. (Royal Society of Chemistry)
    Single-walled carbon nanotubes (SWCNTs) were successfully solubilized using water-sol. p-phosphonated calix[n]arenes (n = 4, 6, 8) and extended arm' upper rim functionalized (benzyl, phenyl) p-sulfonated calix[8]arenes. Selective SWCNT diam. solubilization was demonstrated and subsequent preferential enrichment of SWCNTs with semiconducting or metallic electronic properties was achieved. These water-sol. supramol. systems can be incorporated into post-growth purifn. protocols with direct implications in areas such as nano-electronics and device fabrication.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXhsVCnu7fP&md5=f9ced9bdf62680431daec043fbeffbd6
  28. 28
    Maity, D.; Kumar, S.; Curreli, F.; Debnath, A. K.; Hamilton, A. D. α-Helix-Mimetic Foldamers for Targeting HIV-1 TAR RNA. Chem. - Eur. J. 2019, 25, 7265– 7269,  DOI: 10.1002/chem.201900139
    [Crossref], [PubMed], [CAS], Google Scholar
    28
    α-Helix-Mimetic Foldamers for Targeting HIV-1 TAR RNA
    Maity, Debabrata; Kumar, Sunil; Curreli, Francesca; Debnath, Asim K.; Hamilton, Andrew D.
    Chemistry - A European Journal (2019), 25 (30), 7265-7269CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)
    An oligopyridylamide-based foldamer approach has been employed to target HIV TAR RNA-TAT assembly as a model system to study RNA-protein interactions. The oligopyridylamide scaffold adopts a constrained conformation which presents surface functionalities at distinct spatial locations and mimic the chem. features of the secondary structure of proteins. We have designed a library of oligopyridylamides contg. diverse surface functionalities which mimic the side chain residues of the TAT protein domain. The interaction of TAR RNA and TAT plays a pivotal role in facilitating HIV replication. The library was screened using various fluorescent based assays to identify antagonists of the TAR RNA-TAT complex. A tricationic oligopyridylamide ADH-19, possessed the highest affinity towards TAR and efficiently inhibited the TAR RNA-TAT interaction with apparent Kd of 4.1±1.0μM. Spectroscopic studies demonstrated that ADH-19 interacts with the bulge and the lower bulge regions of TAR RNA, the domains important for TAT interaction. ADH-19 demonstrated appreciable in vivo efficacy (IC50=25±1μM) by rescuing TZM-bl cells infected with the pseudovirus HIV-1HXB-2.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXnt1Wisrk%253D&md5=eecbd5a2608cbba31bf3d8b515c71394
  29. 29
    Bruns, C. J.; Liu, H.; Francis, M. B. Near-quantitative aqueous synthesis of rotaxanes via bioconjugation to oligopeptides and proteins. J. Am. Chem. Soc. 2016, 138, 15307– 15310,  DOI: 10.1021/jacs.6b10231
    [ACS Full Text ACS Full Text], [CAS], Google Scholar
    29
    Near-Quantitative Aqueous Synthesis of Rotaxanes via Bioconjugation to Oligopeptides and Proteins
    Bruns, Carson J.; Liu, Hanwei; Francis, Matthew B.
    Journal of the American Chemical Society (2016), 138 (47), 15307-15310CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
    In spite of widespread interest in rotaxane-based mol. machines and materials, rotaxanes have not been attached covalently to proteins. The authors describe the near-quant. aq. synthesis of [2]rotaxanes based on neutral and charged aq. hosts-cucurbit[7]uril (CB7) and cyclobis(paraquat-p-phenylene) (CBPQT4+), resp.-using the thiol-ene addn. of cysteine and maleimide as a stoppering protocol. After verifying the high efficiency of the reaction using glutathione (GSH) as an oligopeptide stopper, the authors have employed cytochrome C (CytC) as a protein stopper to produce the first well-characterized protein-rotaxane bioconjugates. The authors anticipate that this methodol. will enable the prepn. of novel materials that combine the unique properties of proteins and mech. bonds.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhvVaitbfJ&md5=c7560f60b5d49ce857992b331a751ead
  30. 30
    Alex, J. M.; Corvaglia, V.; Hu, X.; Engilberge, S.; Huc, I.; Crowley, P. B. Crystal structure of a protein–aromatic foldamer composite: macromolecular chiral resolution. Chem. Commun. 2019, 55, 11087– 11090,  DOI: 10.1039/C9CC05330A
    [Crossref], [PubMed], [CAS], Google Scholar
    30
    Crystal structure of a protein-aromatic foldamer composite: macromolecular chiral resolution
    Alex, Jimi M.; Corvaglia, Valentina; Hu, Xiaobo; Engilberge, Sylvain; Huc, Ivan; Crowley, Peter B.
    Chemical Communications (Cambridge, United Kingdom) (2019), 55 (74), 11087-11090CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
    Co-crystn. of a 2 kDa tether-free sulfonated foldamer and the 13 kDa lysine-rich cytochrome c yielded a remarkable biohybrid assembly with chiral resoln. of the foldamer helix handedness. In the crystal a ∼5 nm foldamer stack was surrounded by eight mols. of protein. NMR and CD expts. suggest interesting differences in the soln. state recognition processes.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhs1aiur3M&md5=e6f072c4de5fff2323e1c2e61e348aea

Cited By

This article is cited by 7 publications.

  1. Seulgi Kim, Dong Hee Lee, Ki-Min Park, Jong Hwa Jung, Shim Sung Lee, In-Hyeok Park. Unexpected Solvent-Dependent Self-Assembly of Alkali Metal Complexes of Calix[6]-mono-crown-4: Dinuclear Bowls, a Pseudo-Capsule, and a One-Dimensional Polymer. Inorganic Chemistry 2022, 61 (45) , 18213-18220. https://doi.org/10.1021/acs.inorgchem.2c03020
  2. Peter B. Crowley. Protein–Calixarene Complexation: From Recognition to Assembly. Accounts of Chemical Research 2022, 55 (15) , 2019-2032. https://doi.org/10.1021/acs.accounts.2c00206
  3. Aleksandra Kieliszek, Maura Malinska. Conformations of p-tert-Butylcalix[8]arene in Solvated Crystal Structures. Crystal Growth & Design 2021, 21 (12) , 6862-6871. https://doi.org/10.1021/acs.cgd.1c00773
  4. Numan Yuksel, M. Ferdi Fellah. Hydrogen adsorption and sensing properties of p-tert-butylcalix[4]arene and its transition metal complexes: A DFT study. International Journal of Hydrogen Energy 2023, 48 (60) , 23348-23361. https://doi.org/10.1016/j.ijhydene.2022.12.012
  5. Stefano Volpi, Aishling Doolan, Laura Baldini, Alessandro Casnati, Peter B. Crowley, Francesco Sansone. Complex Formation between Cytochrome c and a Tetra-alanino-calix[4]arene. International Journal of Molecular Sciences 2022, 23 (23) , 15391. https://doi.org/10.3390/ijms232315391
  6. Kateryna Kravets, Mykola Kravets, Helena Butkiewicz, Sandra Kosiorek, Volodymyr Sashuk, Oksana Danylyuk. Electrostatic co-assembly of pillar[ n ]pyridiniums and calix[4]arene in aqueous media. CrystEngComm 2022, 24 (12) , 2213-2216. https://doi.org/10.1039/D2CE00232A
  7. B. Gassoumi, F.E. Ben Mohamed, M.E. Castro, F.J. Melendez, A. Karayel, L. Nouar, F. Madi, H. Ghalla, S. Özkınalı, V.I. Kovalenko, R. Ben Chaabane, H. Ben Ouada. In silico exploration of O-H…X2+ (X = Cu, Ag, Hg) interaction, targeted adsorption zone, charge density iso-surface, O-H proton analysis and topographic parameters theory for calix[6]arene and calix[8]arene as model. Journal of Molecular Liquids 2021, 334 , 116127. https://doi.org/10.1016/j.molliq.2021.116127
Download PDF

  • Abstract

    High Resolution Image
    Download MS PowerPoint Slide

    Figure 1

    Figure 1. Sulfonato-calix[8]arene (sclx8) and p-benzyl-sulfonato-calix[8]arene (b-sclx8).

    High Resolution Image
    Download MS PowerPoint Slide

    Figure 2

    Figure 2. Overlaid regions of the 1H–15N HSQC spectra of cyt c in the absence (black contours) and presence of 2 (red) or 4 (blue) equiv of b-sclx8, in 20 mM sodium acetate and 50 mM NaCl, pH 5.6. Note the signal loss at 4 equiv of b-sclx8 due to sample precipitation.

    High Resolution Image
    Download MS PowerPoint Slide

    Figure 3

    Figure 3. (A) The N-terminal α-helix of cyt c inserts into a hydrophobic groove presented by a trimeric stack of b-sclx8. The stack is threaded by PEG (navy) giving rise to pseudorotaxane. The 2Fo-Fc electron density map (contoured at 0.5σ) is shown as a blue mesh. (B) Lys4 and Lys5 interact with the calixarene stack via salt bridges to the sulfonate ions. (C) Crystal packing in the cyt c and b-sclx8 structure. Adjacent pairs of b-sclx8 stacks are in close proximity (<6 Å). Axes denote the unit cells.

    High Resolution Image
    Download MS PowerPoint Slide

  • References

    ARTICLE SECTIONS
    Jump To

    This article references 30 other publications.

    1. 1
      Wells, J. A.; McClendon, C. L. Reaching for high-hanging fruit in drug discovery at protein–protein interfaces. Nature 2007, 450, 1001– 1009,  DOI: 10.1038/nature06526
      [Crossref], [PubMed], [CAS], Google Scholar
      1
      Reaching for high-hanging fruit in drug discovery at protein-protein interfaces
      Wells, James A.; McClendon, Christopher L.
      Nature (London, United Kingdom) (2007), 450 (7172), 1001-1009CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)
      A review. Targeting the interfaces between proteins has huge therapeutic potential, but discovering small-mol. drugs that disrupt protein-protein interactions is an enormous challenge. Several recent success stories, however, indicate that protein-protein interfaces might be more tractable than has been thought. These studies discovered small mols. that bind with drug-like potencies to 'hotspots' on the contact surfaces involved in protein-protein interactions. Remarkably, these small mols. bind deeper within the contact surface of the target protein, and bind with much higher efficiencies, than do the contact atoms of the natural protein partner. Some of these small mols. are now making their way through clin. trials, so this high-hanging fruit might not be far out of reach.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXhsVaqtr7F&md5=e7ed69fd8c362a71c4b99f029c16a6fc
    2. 2
      Luo, Q.; Hou, C.; Bai, Y.; Wang, R.; Liu, J. Protein assembly: versatile approaches to construct highly ordered nanostructures. Chem. Rev. 2016, 116, 13571– 13632,  DOI: 10.1021/acs.chemrev.6b00228
      [ACS Full Text ACS Full Text], [CAS], Google Scholar
      2
      Protein Assembly: Versatile Approaches to Construct Highly Ordered Nanostructures
      Luo, Quan; Hou, Chunxi; Bai, Yushi; Wang, Ruibing; Liu, Junqiu
      Chemical Reviews (Washington, DC, United States) (2016), 116 (22), 13571-13632CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)
      A review. Nature endows life with a wide variety of sophisticated, synergistic and highly functional protein assemblies. Following Nature's inspiration to assemble protein building blocks into exquisite nanostructures is emerging as a fascinating research field. Dictating protein assembly to obtain highly ordered nanostructures and sophisticated functions not only provides a powerful tool to understand the natural protein assembly process, but also offers access to advanced biomaterials. Over the past couple of decades, the field of protein assembly has undergone unexpected and rapid developments, and various innovative strategies have been proposed. This review outlines recent advances in the field of protein assembly and summarizes several strategies, including biotechnol. strategies, chem. strategies, and combinations of these approaches, for manipulating proteins to self-assemble into desired nanostructures. The emergent applications of protein assemblies as versatile platforms to design a wide variety of attractive functional materials with improved performances have also been discussed. The goal of this review is to highlight the importance of this highly interdisciplinary field and to promote its growth in a diverse variety of research fields ranging from nanoscience and material science to synthetic biol.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhsVeksbnO&md5=0802f364ddc303d7f32253d17af670f0
    3. 3
      van Dun, S.; Ottmann, C.; Milroy, L.-G.; Brunsveld, L. Supramolecular chemistry targeting proteins. J. Am. Chem. Soc. 2017, 139, 13960– 13968,  DOI: 10.1021/jacs.7b01979
      [ACS Full Text ACS Full Text], [CAS], Google Scholar
      3
      Supramolecular Chemistry Targeting Proteins
      van Dun, Sam; Ottmann, Christian; Milroy, Lech-Gustav; Brunsveld, Luc
      Journal of the American Chemical Society (2017), 139 (40), 13960-13968CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
      A review. The specific recognition of protein surface elements is a fundamental challenge in the life sciences. New developments in this field will form the basis of advanced therapeutic approaches and lead to applications such as sensors, affinity tags, immobilization techniques, and protein-based materials. Synthetic supramol. mols. and materials are creating new opportunities for protein recognition that are orthogonal to classical small mol. and protein-based approaches. As outlined here, their unique mol. features enable the recognition of amino acids, peptides, and even whole protein surfaces, which can be applied to the modulation and assembly of proteins. The authors believe that structural insights into these processes are of great value for the further development of this field and have therefore focused this Perspective on contributions that provide such structural data.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhsFeit7vL&md5=56422173d029b081e10d773705b8a478
    4. 4
      Supramolecular Protein Chemistry: Assembly, Architecture and Application; Crowley, P. B., Ed.; Royal Society of Chemistry: Cambridge, 2020; pp 1– 312.
      [Crossref], Google Scholar
      There is no corresponding record for this reference.
    5. 5
      Webber, M. J.; Appel, E. A.; Vinciguerra, B.; Cortinas, A. B.; Thapa, L. S.; Jhunjhunwala, S.; Isaacs, L.; Langer, R.; Anderson, D. G. Supramolecular PEGylation of biopharmaceuticals. Proc. Natl. Acad. Sci. U. S. A. 2016, 113, 14189– 14194,  DOI: 10.1073/pnas.1616639113
      [Crossref], [PubMed], [CAS], Google Scholar
      5
      Supramolecular PEGylation of biopharmaceuticals
      Webber, Matthew J.; Appel, Eric A.; Vinciguerra, Brittany; Cortinas, Abel B.; Thapa, Lavanya S.; Jhunjhunwala, Siddharth; Isaacs, Lyle; Langer, Robert; Anderson, Daniel G.
      Proceedings of the National Academy of Sciences of the United States of America (2016), 113 (50), 14189-14194CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)
      The covalent modification of therapeutic biomols. has been broadly explored, leading to a no. of clin. approved modified protein drugs. These modifications are typically intended to address challenges arising in biopharmaceutical practice by promoting improved stability and shelf life of therapeutic proteins in formulation, or modifying pharmacokinetics in the body. Toward these objectives, covalent modification with poly(ethylene glycol) (PEG) has been a common direction. Here, a platform approach to biopharmaceutical modification is described that relies on noncovalent, supramol. host-guest interactions to endow proteins with prosthetic functionality. Specifically, a series of cucurbit[7]uril (CB[7])-PEG conjugates are shown to substantially increase the stability of three distinct protein drugs in formulation. Leveraging the known and high-affinity interaction between CB[7] and an N-terminal arom. residue on one specific protein drug, insulin, further results in altering of its pharmacol. properties in vivo by extending activity in a manner dependent on mol. wt. of the attached PEG chain. Supramol. modification of therapeutic proteins affords a noncovalent route to modify its properties, improving protein stability and activity as a formulation excipient. Furthermore, this offers a modular approach to append functionality to biopharmaceuticals by noncovalent modification with other mols. or polymers, for applications in formulation or therapy.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhvFCnsL%252FN&md5=4a518f1dec10cd5c78c7cbb6e74149db
    6. 6
      de Vink, P. J.; Briels, J. M.; Schrader, T.; Milroy, L.-G.; Brunsveld, L.; Ottmann, C. A binary bivalent supramolecular assembly platform based on cucurbit[8]uril and dimeric adapter protein 14–3-3. Angew. Chem., Int. Ed. 2017, 56, 8998– 9002,  DOI: 10.1002/anie.201701807
      [Crossref], [CAS], Google Scholar
      6
      A binary bivalent supramolecular assembly platform based on cucurbit[8]uril and dimeric adapter protein 14-3-3
      de Vink, Pim J.; Briels, Jeroen M.; Schrader, Thomas; Milroy, Lech-Gustav; Brunsveld, Luc; Ottmann, Christian
      Angewandte Chemie, International Edition (2017), 56 (31), 8998-9002CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
      Interactions between proteins frequently involve recognition sequences based on multivalent binding events. Dimeric 14-3-3 adapter proteins are a prominent example and typically bind partner proteins in a phosphorylation-dependent monovalent or bivalent manner. Here, we describe the development of a cucurbit[8]uril (Q8)-based supramol. system, which in conjunction with the 14-3-3β protein dimer acts as a binary and bivalent protein assembly platform. We fused the Phe-Gly-Gly (FGG) tripeptide motif to the N-terminus of the 14-3-3-binding epitope of the estrogen receptor α (ERα) for selective binding to Q8. Q8-induced dimerization of the ERα epitope augmented its affinity towards 14-3-3β through a binary bivalent binding mode. The crystal structure of the Q8-induced ternary complex revealed mol. insight into the multiple supramol. interactions between the protein, the peptide, and Q8.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhtV2gs7%252FO&md5=0450a9a632f031e42a7db38c7e9d900d
    7. 7
      Guagnini, F.; Engilberge, S.; Ramberg, K. O.; Pérez, J.; Crowley, P. B. Engineered assembly of a protein-cucurbituril biohybrid. Chem. Commun. 2020, 56, 360– 363,  DOI: 10.1039/C9CC07198A
      [Crossref], [PubMed], [CAS], Google Scholar
      7
      Engineered assembly of a protein-cucurbituril biohybrid
      Guagnini, Francesca; Engilberge, Sylvain; Ramberg, Kiefer O.; Perez, Javier; Crowley, Peter B.
      Chemical Communications (Cambridge, United Kingdom) (2020), 56 (3), 360-363CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
      A cryst. biohybrid with a 4 : 1 protein : cucurbituril mass ratio is presented. This result was achieved by engineering addnl. cucurbit[7]uril (Q7) binding sites into a β-propeller protein. In contrast to the parent protein, Q7-controlled assembly of the engineered variant occurred in soln., as evidenced by NMR and SAXS measurements.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXitlWhsb%252FL&md5=7816ef6488835461ce1aa36c24f0ca4f
    8. 8
      Guagnini, F.; Engilberge, S.; Flood, R. J.; Ramberg, K. O.; Crowley, P. B. Metal-mediated protein–cucurbituril crystalline architectures. Cryst. Growth Des. 2020, 20, 6983– 6989,  DOI: 10.1021/acs.cgd.0c01023
      [ACS Full Text ACS Full Text], [CAS], Google Scholar
      8
      Metal-Mediated Protein-Cucurbituril Crystalline Architectures
      Guagnini, Francesca; Engilberge, Sylvain; Flood, Ronan J.; Ramberg, Kiefer O.; Crowley, Peter B.
      Crystal Growth & Design (2020), 20 (10), 6983-6989CODEN: CGDEFU; ISSN:1528-7483. (American Chemical Society)
      Controlled protein assembly is an enabling technol., for example, in the bottom-up fabrication of biomaterials. This paper describes the assembly of a β-propeller protein using two orthogonal interaction modes. Previously, protein assembly was directed by metal coordination or macrocycle complexation. Here, the authors demonstrate the combination of metal coordination and macrocycle complexation for controlled assembly. An established protein-cucurbit[7]uril (Q7) assembly, which relies on trimeric Q7 clusters, was modified by the inclusion of metal-binding sites in the protein. The application of zinc-histidine coordination to tune the Q7-induced assembly resulted in metallo-bioorg. cryst. architectures. The relative arrangement of the protein-Q7 layers was reorganized by the zinc bridging ions. One structure resulted in a different type of protein-Q7 packing that involves Q7 dimers. Apparently, Q7 is a versatile mol. glue that can be combined with metal-mediated protein assembly. This dual strategy expands significantly the toolkit for engineered assembly. A protein-cucurbit[7]uril (Q7) assembly was engineered by the inclusion of zinc-binding sites to yield distinct arrangements of protein-Q7 layers.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhs1KiurzL&md5=e873ee78efefe7d20a31182cdfca1fc0
    9. 9
      McGovern, R. E.; Fernandes, H.; Khan, A. R.; Power, N. P.; Crowley, P. B. Protein camouflage in cytochrome c-calixarene complexes. Nat. Chem. 2012, 4, 527– 533,  DOI: 10.1038/nchem.1342
      [Crossref], [PubMed], [CAS], Google Scholar
      9
      Protein camouflage in cytochrome c-calixarene complexes
      McGovern, Roise E.; Fernandes, Humberto; Khan, Amir R.; Power, Nicholas P.; Crowley, Peter B.
      Nature Chemistry (2012), 4 (7), 527-533CODEN: NCAHBB; ISSN:1755-4330. (Nature Publishing Group)
      Small mols. that recognize protein surfaces are important tools for modifying protein interaction properties. Since the 1980s, several thousand studies concerning calixarenes and host-guest interactions have been published. Although there is growing interest in protein-calixarene interactions, only limited structural information has been available to date. We now report the crystal structure of a protein-calixarene complex. The water-sol. p-sulfonatocalix[4]arene is shown to bind the lysine-rich cytochrome c at three different sites. Binding curves obtained from NMR titrns. reveal an interaction process that involves two or more binding sites. Together, the data indicate a dynamic complex in which the calixarene explores the surface of cytochrome c. In addn. to providing valuable information on protein recognition, the data also indicate that the calixarene is a mediator of protein-protein interactions, with potential applications in generating assemblies and promoting crystn.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xmt1Gqt7Y%253D&md5=36831f24c65387bd400e7e1e5de177b1
    10. 10
      McGovern, R. E.; McCarthy, A. A.; Crowley, P. B. Protein assembly mediated by sulfonatocalix[4]arene. Chem. Commun. 2014, 50, 10412– 10415,  DOI: 10.1039/C4CC04897K
      [Crossref], [PubMed], [CAS], Google Scholar
      10
      Protein assembly mediated by sulfonatocalix[4]arene
      McGovern, Roise E.; McCarthy, Andrew A.; Crowley, Peter B.
      Chemical Communications (Cambridge, United Kingdom) (2014), 50 (72), 10412-10415CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
      A crystal structure of lysozyme in complex with p-sulfonato-calix[4]arene (sclx4) reveals a linear assembly of protein tetramers glued together by protein-calixarene interactions. One interaction involves encapsulation of the highly exposed C-terminal Arg128. The other involves an intricate protein-bound complex of sclx4, Mg2+ and a fragment of polyethylene glycol.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtF2ksLjF&md5=5c8a69a3208c78f9c8e91bd8ad13ba81
    11. 11
      Rennie, M. L.; Doolan, A. M.; Raston, C. L.; Crowley, P. B. Protein dimerization on a phosphonated calix[6]arene disc. Angew. Chem., Int. Ed. 2017, 56, 5517– 5521,  DOI: 10.1002/anie.201701500
      [Crossref], [CAS], Google Scholar
      11
      Protein dimerization on a phosphonated calix[6]arene disc
      Rennie, Martin L.; Doolan, Aishling M.; Raston, Colin L.; Crowley, Peter B.
      Angewandte Chemie, International Edition (2017), 56 (20), 5517-5521CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
      Complex formation between cationic cytochrome c and the water-sol., poly-anionic p-phosphonatocalix[6]arene (pclx6) was investigated. A crystal structure (at 1.8 Å resoln.) revealed a remarkable dimeric disk of pclx6 that acts like glue to mediate a sym. (C2) protein dimer. The calixarene disk had a diam. of ∼1.5 nm and masked ∼360 Å2 of the protein surface. The key protein-calixarene contacts occurred via 2 linchpin Lys residues, with addnl. contacts provided by a small hydrophobic patch. The protein-calixarene supramol. assemblies were obsd. in soln. by size-exclusion chromatog. with multi-angle light scattering and NMR spectroscopy. Using isothermal titrn. calorimetry and NMR data, an apparent Kd in the low micromolar range was detd. for the charge-rich protein-calixarene complex. In contrast to p-sulfonatocalix[4]arene, the larger pclx6 had a single, well-defined binding site that mediated the assembly of cytochrome c in soln.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXmtVyhurs%253D&md5=68aaa93576986b1a0eacfd07838c7ddc
    12. 12
      Doolan, A. M.; Rennie, M. L.; Crowley, P. B. Protein recognition by functionalized sulfonato-calix[4]arenes. Chem. - Eur. J. 2018, 24, 984– 991,  DOI: 10.1002/chem.201704931
      [Crossref], [PubMed], [CAS], Google Scholar
      12
      Protein recognition by functionalized sulfonatocalix[4]arenes
      Doolan, Aishling M.; Rennie, Martin L.; Crowley, Peter B.
      Chemistry - A European Journal (2018), 24 (4), 984-991CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)
      The interactions of 2 mono-functionalized sulfonatocalix[4]arenes with cytochrome c were investigated by structural and thermodn. methods. The replacement of a single sulfonate with either a bromo or a Ph substituent resulted in altered recognition of cytochrome c as evidenced by x-ray crystallog. The bromo-substituted ligand yielded a new binding mode in which a self-encapsulated calixarene dimer contributed to crystal packing. This ligand also formed a weak halogen bond with the protein. The phenyl-substituted ligand was bound to Lys-4 of cytochrome c, in a 1.7 Å-resoln. crystal structure. A dimeric packing arrangement mediated by ligand-ligand contacts in the crystal suggested a possible assembly mechanism. The different protein recognition properties of these calixarenes were discussed.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhvFyjs7jM&md5=14cd0dccf75aabe744b6d9c4bfb0faab
    13. 13
      Alex, J. M.; Rennie, M. L.; Volpi, S.; Sansone, F.; Casnati, A.; Crowley, P. B. Phosphonated calixarene as a “molecular glue” for protein crystallization. Cryst. Growth Des. 2018, 18, 2467– 2473,  DOI: 10.1021/acs.cgd.8b00092
      [ACS Full Text ACS Full Text], [CAS], Google Scholar
      13
      Phosphonated Calixarene as a "Molecular Glue" for Protein Crystallization
      Alex, Jimi M.; Rennie, Martin L.; Volpi, Stefano; Sansone, Francesco; Casnati, Alessandro; Crowley, Peter B.
      Crystal Growth & Design (2018), 18 (4), 2467-2473CODEN: CGDEFU; ISSN:1528-7483. (American Chemical Society)
      Protein crystn. remains a serious bottleneck to structure detn. by X-ray diffraction methods. Compds. acting as "mol. glue" provide a promising strategy to overcome this bottleneck. Such mols. interact via noncovalent bonds with two or more protein surfaces to promote lattice formation. Here, we report a 1.5 Å resoln. crystal structure of lysine-rich cytochrome c complexed with p-phosphonatomethyl-calix[4]arene (pmclx4). Evidence for complex formation in soln. was provided by NMR studies. Similar to p-sulfonato-calix[4]arene (sclx4), the cavity of pmclx4 entrapped a single lysine side chain. Interesting features of protein recognition by the phosphonate substituents were identified in the crystal structure. A new calixarene binding site was identified at Lys54. The electron d. at this site indicated two distinct calixarene conformers, suggesting a degree of ligand mobility. The role of pmclx4 in protein crystal packing (mol. glue and patchy particle model) as well as differences in protein-binding with respect to sclx4 are discussed.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXks1yiu7c%253D&md5=5cc8b55005f39d13b646bb0ecaf55182
    14. 14
      Rennie, M. L.; Fox, G. C.; Pérez, J.; Crowley, P. B. Auto-regulated protein assembly on a supramolecular scaffold. Angew. Chem., Int. Ed. 2018, 57, 13764– 13769,  DOI: 10.1002/anie.201807490
      [Crossref], [CAS], Google Scholar
      14
      Auto-regulated Protein Assembly on a Supramolecular Scaffold
      Rennie, Martin L.; Fox, Gavin C.; Perez, Javier; Crowley, Peter B.
      Angewandte Chemie, International Edition (2018), 57 (42), 13764-13769CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
      Controlled protein assembly provides a means to regulate function. Supramol. building blocks, including rigid macrocycles, are versatile triggers of protein assembly. Now it is shown that sulfonato-calix[8]arene (sclx8) mediates the formation of cytochrome c tetramers in soln. This tetramer spontaneously disassembles at ≥2 equiv of sclx8, providing a remarkable example of auto-regulation. Using X-ray crystallog. the sclx8 binding sites on cytochrome c were characterized. Crystal structures at different protein-ligand ratios reveal varying degrees (up to 35 %) of protein surface coverage by the flexible calixarene and suggest a mechanism for oligomer disassembly. The soln. structure of the oligomer was characterized by small-angle X-ray scattering. Overall, the data indicate calixarene-controlled protein assembly and disassembly without the requirement for a competitive inhibitor, and point to protein encapsulation by a flexible macrocycle.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhslWjurjE&md5=479efd470dec2b3bf8798c0218ab7613
    15. 15
      Mummidivarapu, V. V. S.; Rennie, M. L.; Doolan, A. M.; Crowley, P. B. Noncovalent PEGylation via sulfonatocalix[4]arene - A crystallographic proof. Bioconjugate Chem. 2018, 29, 3999– 4003,  DOI: 10.1021/acs.bioconjchem.8b00769
      [ACS Full Text ACS Full Text], [CAS], Google Scholar
      15
      Noncovalent PEGylation via sulfonatocalix[4]arene - A crystallographic proof
      Mummidivarapu, V. V. Sreenivasu; Rennie, Martin L.; Doolan, Aishling M.; Crowley, Peter B.
      Bioconjugate Chemistry (2018), 29 (12), 3999-4003CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)
      Noncovalent or supramol. PEGylation, in combination with the site of administration, has great potential to increase the half-life of therapeutic proteins. To date, a variety of noncovalent PEGylation strategies have been devised. However, questions remain concerning the nature of the protein-poly(ethylene glycol) (PEG) interaction. Here, we report structural analyses of a model system that comprised Lys-rich cytochrome c and 2 PEGylated variants of sulfonatocalix[4]arene. Complex formation was characterized in soln. by NMR spectroscopy. It was found that mono- or di-PEGylated sulfonatocalix[4]arene bound the protein similar to the parent calixarene. X-ray crystal structures at <2.7 Å resoln. of the PEGylated derivs. in complex with cytochrome c revealed that the PEG chains were mostly disordered or encapsulated within the calixarene cavity. These results suggest that there was minimal interaction between the PEG and the protein surface, providing further evidence in favor of PEG maintaining a random coil conformation.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXit1Wmur7J&md5=5b579dea529386fb7f433bd6e4f59bbb
    16. 16
      Alex, J. M.; Rennie, M. L.; Engilberge, S.; Lehoczki, G.; Dorottya, H.; Fizil, A.; Batta, G.; Crowley, P. B. Calixarene-mediated assembly of a small antifungal protein. IUCrJ 2019, 6, 238– 247,  DOI: 10.1107/S2052252519000411
      [Crossref], [PubMed], [CAS], Google Scholar
      16
      Calixarene-mediated assembly of a small antifungal protein
      Alex, Jimi M.; Rennie, Martin L.; Engilberge, Sylvain; Lehoczki, Gabor; Dorottya, Hajdu; Fizil, Adam; Batta, Gyula; Crowley, Peter B.
      IUCrJ (2019), 6 (2), 238-247CODEN: IUCRAJ; ISSN:2052-2525. (International Union of Crystallography)
      Synthetic macrocycles such as calixarenes and cucurbiturils are increasingly applied as mediators of protein assembly and crystn. The macrocycle can facilitate assembly by providing a surface on which two or more proteins bind simultaneously. This work explores the capacity of the sulfonato-calix[n]arene (sclxn) series to effect crystn. of PAF, a small, cationic antifungal protein. Co-crystn. with sclx4, sclx6 or sclx8 led to high-resoln. crystal structures. In the absence of sclxn, diffraction-quality crystals of PAF were not obtained. Interestingly, all three sclxn were bound to a similar patch on PAF. The largest and most flexible variant, sclx8, yielded a dimer of PAF. Complex formation was evident in soln. via NMR and ITC expts., showing more pronounced effects with increasing macrocycle size. In agreement with the crystal structure, the ITC data suggested that sclx8 acts as a bidentate ligand. The contributions of calixarene size/conformation to protein recognition and assembly are discussed. Finally, it is suggested that the conserved binding site for anionic calixarenes implicates this region of PAF in membrane binding, which is a prerequisite for antifungal activity.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXksVajtr8%253D&md5=71ee504263ead42d06de3c8a11d1fd44
    17. 17
      Engilberge, S.; Rennie, M. L.; Crowley, P. B. Calixarene Capture of Partially Unfolded Cytochrome c. FEBS Lett. 2019, 593, 2112– 2117,  DOI: 10.1002/1873-3468.13512
      [Crossref], [PubMed], [CAS], Google Scholar
      17
      Calixarene capture of partially unfolded cytochrome c
      Engilberge, Sylvain; Rennie, Martin L.; Crowley, Peter B.
      FEBS Letters (2019), 593 (16), 2112-2117CODEN: FEBLAL; ISSN:0014-5793. (Wiley-Blackwell)
      Supramol. receptors such as water-sol. calixarenes are in development as 'mol. glues' for protein assembly. Here, we obtained cocrystals of sulfonato-calix[6]arene (sclx6) and yeast cytochrome c (cytc) in the presence of imidazole. A crystal structure at 2.65 Å resoln. reveals major structural rearrangement and disorder in imidazole-bound cytc. The largest protein-calixarene interface involves 440 Å2 of the protein surface with key contacts at Arg13, Lys73, and Lys79. These lysines participate in alk. transitions of cytc and are part of Ω-loop D, which is substantially restructured in the complex with sclx6. The structural modification also includes Ω-loop C, which is disordered (residues 41-55 inclusive). These results suggest the possibility of using supramol. scaffolds to trap partially disordered proteins.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhtlamu7nI&md5=7b9cc49d6ba9396737a32787e49c5727
    18. 18
      Engilberge, S.; Rennie, M. L.; Dumont, E.; Crowley, P. B. Tuning protein frameworks via auxiliary supramolecular interactions. ACS Nano 2019, 13, 10343– 10350,  DOI: 10.1021/acsnano.9b04115
      [ACS Full Text ACS Full Text], [CAS], Google Scholar
      18
      Tuning Protein Frameworks via Auxiliary Supramolecular Interactions
      Engilberge, Sylvain; Rennie, Martin L.; Dumont, Elise; Crowley, Peter B.
      ACS Nano (2019), 13 (9), 10343-10350CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)
      Protein crystals with their precise, periodic array of functional building blocks have potential applications in biomaterials, sensing, and catalysis. This paper describes how a highly porous cryst. framework of a cationic redox protein and an anionic macrocycle can be modulated by a small cationic effector. Ternary composites of protein (∼13 kDa), calix[8]arene (∼1.5 kDa), and effector (∼0.2 kDa) formed distinct cryst. architectures, dependent on the effector concn. and the crystn. technique. A combination of X-ray crystallog. and d. functional theory (DFT) calcns. was used to decipher the framework variations, which appear to be dependent on a calixarene conformation change mediated by the effector. This "switch" calixarene was obsd. in three states, each of which is assocd. with a different interaction network. Two structures obtained by co-crystn. with the effector contained an addnl. protein "pillar", resulting in framework duplication and decreased porosity. These results suggest how protein assembly can be engineered by supramol. host-guest interactions.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhslegtLzM&md5=7c36109bdf1fe9d43d633c25320a98e4
    19. 19
      Alex, J. M.; Brancatelli, G.; Volpi, S.; Bonaccorso, C.; Casnati, A.; Geremia, S.; Crowley, P. B. Probing the determinants of porosity in protein frameworks: co-crystals of cytochrome c and an octaanionic calix[4]arene. Org. Biomol. Chem. 2020, 18, 211– 214,  DOI: 10.1039/C9OB02275A
      [Crossref], [PubMed], [CAS], Google Scholar
      19
      Probing the determinants of porosity in protein frameworks: co-crystals of cytochrome c and an octa-anionic calix[4]arene
      Alex, Jimi M.; Brancatelli, Giovanna; Volpi, Stefano; Bonaccorso, Carmela; Casnati, Alessandro; Geremia, Silvano; Crowley, Peter B.
      Organic & Biomolecular Chemistry (2020), 18 (2), 211-214CODEN: OBCRAK; ISSN:1477-0520. (Royal Society of Chemistry)
      Sulfonato-calix[n]arenes (sclxn) are promising tools to generate cryst. protein frameworks. We report, for the first time, a lower rim functionalized octa-anionic calix[4]arene (sclx4mc) in complex with proteins. Two crystal structures of sclx4mc bound to yeast or horse heart cytochrome c (cytc) are described. Highly porous honeycomb or tubular assemblies were obtained with yeast or horse cytc, resp. Related frameworks were obtained previously with sclx8 and sclx6 but not with sclx4, suggesting that the ligand charge is a detg. factor.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXitlWhsLfN&md5=e964ed7e524cc096bf51d8152b62cc73
    20. 20
      Ramberg, K. O.; Engilberge, S.; Skorek, T.; Crowley, P. B. Facile fabrication of protein-macrocycle frameworks. J. Am. Chem. Soc. 2021,  DOI: 10.1021/jacs.0c10697
      [ACS Full Text ACS Full Text], Google Scholar
      There is no corresponding record for this reference.
    21. 21
      Abascal, N. C.; Regan, L. The past, present and future of protein-based materials. Open Biol. 2018, 8, 180113,  DOI: 10.1098/rsob.180113
      [Crossref], [PubMed], [CAS], Google Scholar
      21
      The past, present and future of protein-based materials
      Abascal, Nadia C.; Regan, Lynne
      Open Biology (2018), 8 (10), 180113CODEN: OBPICQ; ISSN:2046-2441. (Royal Society)
      A review. Protein-based materials are finding new uses and applications after millennia of impacting the daily life of humans. Some of the earliest uses of protein-based materials are still evident in silk and wool textiles and leather goods. Today, even as silks, wools and leathers are still be used in traditional ways, these proteins are now seen as promising materials for biomaterials, vehicles of drug delivery and components of high-tech fabrics. With the advent of biosynthetic methods and streamlined means of protein purifn., protein-based materials-recombinant and otherwise-are being used in a host of applications at the cutting edge of medicine, electronics, materials science and even fashion. This commentary aims to discuss a handful of these applications while taking a crit. look at where protein-based materials may be used in the future.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXpsFelsbs%253D&md5=939fe952bdff35b894425d2a9dab0817
    22. 22
      Yamagishi, T.-A.; Kawahara, A.; Kita, J.; Hoshima, M.; Umehara, A.; Ishida, S.-I.; Nakamoto, Y. In situ polycondensation of p-tert-butylphenol in the presence of poly(ethylene glycol)s for preparation of polyrotaxanes. Macromolecules 2001, 34, 6565– 6570,  DOI: 10.1021/ma010033e
      [ACS Full Text ACS Full Text], [CAS], Google Scholar
      22
      In Situ Polycondensation of p-tert-Butylphenol in the Presence of Poly(ethylene glycol)s for Preparation of Polyrotaxanes
      Yamagishi, Tada-Aki; Kawahara, Akihiko; Kita, Junko; Hoshima, Miho; Umehara, Ayako; Ishida, Shin-ichiro; Nakamoto, Yoshiaki
      Macromolecules (2001), 34 (19), 6565-6570CODEN: MAMOBX; ISSN:0024-9297. (American Chemical Society)
      A new polyrotaxane was formed by the polycondensation of p-tert-butylphenol (BP) with paraformaldehyde in the presence of poly(ethylene glycol)s, (PEG)s, of various mol. wts. The polyrotaxane of BP oligomers with PEG was obtained when the PEG of av. mol. wts. between 1000 and 10,000 were used in the polycondensation. The polyrotaxane yield and the compn. were dependent on the mol. wt. of PEG. The mol. structure was detd. by FT-IR and 1H NMR spectroscopies and the thermal properties by DSC measurements. 1H NMR spectra of the complexes showed a pair of doublets in the methylene region, which correspond to the methylene protons between phenolic rings in p-tert-butylcalixarenes. The FT-IR spectra and DSC curves were different from those of the blend of linear p-tert-butylphenolic resins with PEG and pure p-tert-butylcalix[8]arene, resp. Calixarenes slipped off the backbone PEG by heating the polyrotaxane in ethylene glycol at 180°. The structure of the dethreaded calixarenes was detd. by 1H NMR, and they were found to be p-tert-butylcalix[8]arenes and a few p-tert-butylcalix[4]arenes. From the characteristic results it was found that the polyrotaxane obtained by the in situ polycondensation of BP was composed of p-tert-butylcalix[8]arenes penetrated by PEG; i.e., this was a calix[8]arene-based polyrotaxane.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3MXlvFamsrg%253D&md5=276a3be2167028332f4ee93016b872c3
    23. 23
      Gaeta, C.; Talotta, C.; Margarucci, L.; Casapullo, A.; Neri, P. Through-the-annulus threading of the larger calix[8]arene macrocycle. J. Org. Chem. 2013, 78, 7627– 7638,  DOI: 10.1021/jo401206j
      [ACS Full Text ACS Full Text], [CAS], Google Scholar
      23
      Through-the-Annulus Threading of the Larger Calix[8]arene Macrocycle
      Gaeta, Carmine; Talotta, Carmen; Margarucci, Luigi; Casapullo, Agostino; Neri, Placido
      Journal of Organic Chemistry (2013), 78 (15), 7627-7638CODEN: JOCEAH; ISSN:0022-3263. (American Chemical Society)
      A complete study of the through-the-annulus threading of the larger calix[8]arene macrocycle with di-n-alkylammonium cations was performed in the presence of the superweak TFPB counterion. Thus, such threading occurs only upon partial preorganization of the calix[8]arene macroring by intramol. bridging. In particular, 1,5-bridged calix[8]arenes with a meta- or para-xylylene bridge (I and II) gave pseudo[2]rotaxanes in which one dialkylammonium axle was threaded into one of the two subcavities of the calix[8]-wheel. Conformational studies by using chem. shift surface maps and DFT calcns. evidenced a 3/4-cone geometry for these subcavities. Higher pseudorotaxane Kass values were obtained for calix[8]-wheels I and II with respect to calix[6]-host III, due to the cooperative effect of their two subcavities. Dynamic NMR studies on calix[8]-pseudorotaxanes evidenced a direct correlation between Kass (and ΔGass) values and energy barriers for calix inversion due to the effectiveness of thread templation. In accordance with DFT calcns., an endo-alkyl preference, over the endo-benzyl one, was obsd. by threading calix[8]-wheel II with the directional n-butylbenzylammonium axle.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtVKqt7jP&md5=bf2eaeb0567f03801437ade7d3c64605
    24. 24
      Stoddart, J. F. Mechanically interlocked molecules (MIMs) – Molecular Shuttles, Switches, and Machines (Nobel Lecture). Angew. Chem., Int. Ed. 2017, 56, 11094– 11125,  DOI: 10.1002/anie.201703216
      [Crossref], [CAS], Google Scholar
      24
      Mechanically Interlocked Molecules (MIMs)-Molecular Shuttles, Switches, and Machines (Nobel Lecture)
      Stoddart, J. Fraser
      Angewandte Chemie, International Edition (2017), 56 (37), 11094-11125CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
      An autobiog. for J. Fraser Stoddart, born May 24, 1942 in Edinburgh, United Kingdom, is presented. Stoddart is a professor of chem. and head of the Stoddart Mechanostereochem. Group at Northwestern University in the United States.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhtlCnsbzI&md5=d5a5e6f75cac3988ee716fb2423bc519
    25. 25
      Gaeta, C.; Talotta, C.; Neri, P. Calix[6]arene-based atropoisomeric pseudo[2]rotaxanes. Beilstein J. Org. Chem. 2018, 14, 2112– 2124,  DOI: 10.3762/bjoc.14.186
      [Crossref], [PubMed], [CAS], Google Scholar
      25
      Calix[6]arene-based atropoisomeric pseudo[2]rotaxanes
      Gaeta, Carmine; Talotta, Carmen; Neri, Placido
      Beilstein Journal of Organic Chemistry (2018), 14 (), 2112-2124CODEN: BJOCBH; ISSN:1860-5397. (Beilstein-Institut zur Foerderung der Chemischen Wissenschaften)
      Some examples of atropisomeric pseudorotaxanes in which the isomerism arises by the different conformations adopted by the wheel are reported here. Upon threading hexahexyloxycalix[6]arene I (R = n-C6H13) with ammonium axles II (R1 = Ph or trifluoromethyl) resp., two atropisomeric pseudorotaxanes were formed in which the calix[6]-wheel I adopts the 1,2,3-alternate and cone conformations. The interconversion between them cannot be obtained by simple rotation around the ArCH2Ar bonds of the calixarene wheel, which is blocked by the presence of the axle inside its cavity. Therefore, it can only be obtained through a mechanism of de-threading/re-threading of the axle. In all the examd. cases, the 1,2,3-alternate and cone atropisomers are, resp., the kinetic and thermodn. ones.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhvFyrt7bK&md5=3bb0951056533a8e564f8c5f75cbbeec
    26. 26
      Orlandini, G.; Casimiro, L.; Bazzoni, M.; Cogliati, B.; Credi, A.; Lucarini, M.; Silvi, S.; Arduini, A.; Secchi, A. Synthesis and properties of a redox-switchable calix[6]arene-based molecular lasso. Org. Chem. Front. 2020, 7, 648– 659,  DOI: 10.1039/C9QO01379B
      [Crossref], [CAS], Google Scholar
      26
      Synthesis and properties of a redox-switchable calix[6]arene-based molecular lasso
      Orlandini, Guido; Casimiro, Lorenzo; Bazzoni, Margherita; Cogliati, Beatrice; Credi, Alberto; Lucarini, Marco; Silvi, Serena; Arduini, Arturo; Secchi, Andrea
      Organic Chemistry Frontiers (2020), 7 (4), 648-659CODEN: OCFRA8; ISSN:2052-4129. (Royal Society of Chemistry)
      The synthesis and characterization of calix[6]arene-based lasso-like mol. structures is described. These interwoven structures consist of an electrochem. responsive N,N'-dialkylviologen arm covalently anchored at the upper rim of a triphenylureido calix[6]arene-based wheel. Upon redn. of the viologen core, a hollow tridimensional macrocyclic structure can be generated. This process is reversible, and the original lasso-like structure can be regenerated by oxidizing the viologen arm to its original dicationic form. Electrochem. and EPR techniques investigated the ability of the system to perform threading/dethreading movements upon redox switching. The functionalization of the arm ω-hydroxy ending with a bulky diphenylacetyl group converts the self-threaded structure in a blocked interwoven mol. compd. belonging to the class of [1]rotaxanes. The ability to form dimeric structures in the shape of a [c2]daisy chain was also demonstrated, an unprecedented result for calixarene macrocycles.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhvF2lsw%253D%253D&md5=6c58706d05589f780d5b3ffab4fa03ae
    27. 27
      Hubble, L. J.; Clark, T. E.; Makha, M.; Raston, C. L. Selective diameter uptake of single-walled carbon nanotubes in water using phosphonated calixarenes and ‘extended arm’ sulfonated calixarenes. J. Mater. Chem. 2008, 18, 5961– 5966,  DOI: 10.1039/b814904f
      [Crossref], [CAS], Google Scholar
      27
      Selective diameter uptake of single-walled carbon nanotubes in water using phosphonated calixarenes and extended arm' sulfonated calixarenes
      Hubble, Lee J.; Clark, Thomas E.; Makha, Mohamed; Raston, Colin L.
      Journal of Materials Chemistry (2008), 18 (48), 5961-5966CODEN: JMACEP; ISSN:0959-9428. (Royal Society of Chemistry)
      Single-walled carbon nanotubes (SWCNTs) were successfully solubilized using water-sol. p-phosphonated calix[n]arenes (n = 4, 6, 8) and extended arm' upper rim functionalized (benzyl, phenyl) p-sulfonated calix[8]arenes. Selective SWCNT diam. solubilization was demonstrated and subsequent preferential enrichment of SWCNTs with semiconducting or metallic electronic properties was achieved. These water-sol. supramol. systems can be incorporated into post-growth purifn. protocols with direct implications in areas such as nano-electronics and device fabrication.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXhsVCnu7fP&md5=f9ced9bdf62680431daec043fbeffbd6
    28. 28
      Maity, D.; Kumar, S.; Curreli, F.; Debnath, A. K.; Hamilton, A. D. α-Helix-Mimetic Foldamers for Targeting HIV-1 TAR RNA. Chem. - Eur. J. 2019, 25, 7265– 7269,  DOI: 10.1002/chem.201900139
      [Crossref], [PubMed], [CAS], Google Scholar
      28
      α-Helix-Mimetic Foldamers for Targeting HIV-1 TAR RNA
      Maity, Debabrata; Kumar, Sunil; Curreli, Francesca; Debnath, Asim K.; Hamilton, Andrew D.
      Chemistry - A European Journal (2019), 25 (30), 7265-7269CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)
      An oligopyridylamide-based foldamer approach has been employed to target HIV TAR RNA-TAT assembly as a model system to study RNA-protein interactions. The oligopyridylamide scaffold adopts a constrained conformation which presents surface functionalities at distinct spatial locations and mimic the chem. features of the secondary structure of proteins. We have designed a library of oligopyridylamides contg. diverse surface functionalities which mimic the side chain residues of the TAT protein domain. The interaction of TAR RNA and TAT plays a pivotal role in facilitating HIV replication. The library was screened using various fluorescent based assays to identify antagonists of the TAR RNA-TAT complex. A tricationic oligopyridylamide ADH-19, possessed the highest affinity towards TAR and efficiently inhibited the TAR RNA-TAT interaction with apparent Kd of 4.1±1.0μM. Spectroscopic studies demonstrated that ADH-19 interacts with the bulge and the lower bulge regions of TAR RNA, the domains important for TAT interaction. ADH-19 demonstrated appreciable in vivo efficacy (IC50=25±1μM) by rescuing TZM-bl cells infected with the pseudovirus HIV-1HXB-2.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXnt1Wisrk%253D&md5=eecbd5a2608cbba31bf3d8b515c71394
    29. 29
      Bruns, C. J.; Liu, H.; Francis, M. B. Near-quantitative aqueous synthesis of rotaxanes via bioconjugation to oligopeptides and proteins. J. Am. Chem. Soc. 2016, 138, 15307– 15310,  DOI: 10.1021/jacs.6b10231
      [ACS Full Text ACS Full Text], [CAS], Google Scholar
      29
      Near-Quantitative Aqueous Synthesis of Rotaxanes via Bioconjugation to Oligopeptides and Proteins
      Bruns, Carson J.; Liu, Hanwei; Francis, Matthew B.
      Journal of the American Chemical Society (2016), 138 (47), 15307-15310CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
      In spite of widespread interest in rotaxane-based mol. machines and materials, rotaxanes have not been attached covalently to proteins. The authors describe the near-quant. aq. synthesis of [2]rotaxanes based on neutral and charged aq. hosts-cucurbit[7]uril (CB7) and cyclobis(paraquat-p-phenylene) (CBPQT4+), resp.-using the thiol-ene addn. of cysteine and maleimide as a stoppering protocol. After verifying the high efficiency of the reaction using glutathione (GSH) as an oligopeptide stopper, the authors have employed cytochrome C (CytC) as a protein stopper to produce the first well-characterized protein-rotaxane bioconjugates. The authors anticipate that this methodol. will enable the prepn. of novel materials that combine the unique properties of proteins and mech. bonds.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhvVaitbfJ&md5=c7560f60b5d49ce857992b331a751ead
    30. 30
      Alex, J. M.; Corvaglia, V.; Hu, X.; Engilberge, S.; Huc, I.; Crowley, P. B. Crystal structure of a protein–aromatic foldamer composite: macromolecular chiral resolution. Chem. Commun. 2019, 55, 11087– 11090,  DOI: 10.1039/C9CC05330A
      [Crossref], [PubMed], [CAS], Google Scholar
      30
      Crystal structure of a protein-aromatic foldamer composite: macromolecular chiral resolution
      Alex, Jimi M.; Corvaglia, Valentina; Hu, Xiaobo; Engilberge, Sylvain; Huc, Ivan; Crowley, Peter B.
      Chemical Communications (Cambridge, United Kingdom) (2019), 55 (74), 11087-11090CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)
      Co-crystn. of a 2 kDa tether-free sulfonated foldamer and the 13 kDa lysine-rich cytochrome c yielded a remarkable biohybrid assembly with chiral resoln. of the foldamer helix handedness. In the crystal a ∼5 nm foldamer stack was surrounded by eight mols. of protein. NMR and CD expts. suggest interesting differences in the soln. state recognition processes.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhs1aiur3M&md5=e6f072c4de5fff2323e1c2e61e348aea

  • Supporting Information

    Supporting Information

    ARTICLE SECTIONS
    Jump To

    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.cgd.0c01717.

    • Experimental details, electron density maps and X-ray data collection, processing, and refinement statistics (PDF)


    Terms & Conditions

    Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

PDF [ 3MB]

Pair your accounts.

Export articles to Mendeley

Get article recommendations from ACS based on references in your Mendeley library.

Pair your accounts.

Export articles to Mendeley

Get article recommendations from ACS based on references in your Mendeley library.

You’ve supercharged your research process with ACS and Mendeley!

STEP 1:
Click to create an ACS ID

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

MENDELEY PAIRING EXPIRED
Your Mendeley pairing has expired. Please reconnect