19F NMR Spectroscopy for the Analysis of RNA Secondary Structure Populations
Abstract

Labeling of RNA with site-specific fluorine atoms has become straightforward in recent years and in particular has become an integrated part of engineered functional RNA with therapeutic potential, e.g. for siRNA technologies. Here, we demonstrate that temperature-dependent one-dimensional 19F NMR spectroscopy of oligoribonucleotides is a powerful tool to obtain direct information on the conformational behavior. The approach is particularly useful for the quantification of monomolecular vs bimolecular secondary structure equilibria.
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- Asmo Aro-Heinilä, Assi Lepistö, Antti Äärelä, Tuomas Antti Lönnberg, Pasi Virta. 2-Trifluoromethyl-6-mercurianiline Nucleotide, a Sensitive 19F NMR Probe for Hg(II)-mediated Base Pairing. The Journal of Organic Chemistry 2022, 87 (1) , 137-146. https://doi.org/10.1021/acs.joc.1c02056
- Andrei Ursu, Kye Won Wang, Jessica A. Bush, Shruti Choudhary, Jonathan L. Chen, Jared T. Baisden, Yong-Jie Zhang, Tania F. Gendron, Leonard Petrucelli, Ilyas Yildirim, Matthew D. Disney. Structural Features of Small Molecules Targeting the RNA Repeat Expansion That Causes Genetically Defined ALS/FTD. ACS Chemical Biology 2020, 15 (12) , 3112-3123. https://doi.org/10.1021/acschembio.0c00049
- Qiang Li, Jialiang Chen, Marko Trajkovski, Yifei Zhou, Chaochao Fan, Kuan Lu, Pingping Tang, Xuncheng Su, Janez Plavec, Zhen Xi, Chuanzheng Zhou. 4′-Fluorinated RNA: Synthesis, Structure, and Applications as a Sensitive 19F NMR Probe of RNA Structure and Function. Journal of the American Chemical Society 2020, 142 (10) , 4739-4748. https://doi.org/10.1021/jacs.9b13207
- Asmo Aro-Heinilä, Tuomas Lönnberg, Pasi Virta. 3-Fluoro-2-mercuri-6-methylaniline Nucleotide as a High-Affinity Nucleobase-Specific Hybridization Probe. Bioconjugate Chemistry 2019, 30 (8) , 2183-2190. https://doi.org/10.1021/acs.bioconjchem.9b00405
- Huan Meng, Lixian Wen, Zhenchuang Xu, Yipeng Li, Jian Hao, Yanchuan Zhao. Nonafluoro-tert-butoxylation of Diaryliodonium Salts. Organic Letters 2019, 21 (13) , 5206-5210. https://doi.org/10.1021/acs.orglett.9b01813
- Zhenchuang Xu, Chao Liu, Shujuan Zhao, Si Chen, Yanchuan Zhao. Molecular Sensors for NMR-Based Detection. Chemical Reviews 2019, 119 (1) , 195-230. https://doi.org/10.1021/acs.chemrev.8b00202
- Takumi Ishizuka, Atsushi Yamashita, Yujiro Asada, and Yan Xu . Studying DNA G-Quadruplex Aptamer by 19F NMR. ACS Omega 2017, 2 (12) , 8843-8848. https://doi.org/10.1021/acsomega.7b01405
- Agata Olszewska, Radek Pohl, and Michal Hocek . Trifluoroacetophenone-Linked Nucleotides and DNA for Studying of DNA–Protein Interactions by 19F NMR Spectroscopy. The Journal of Organic Chemistry 2017, 82 (21) , 11431-11439. https://doi.org/10.1021/acs.joc.7b01920
- Lotta Granqvist and Pasi Virta . 2′-O-[(4-CF3-triazol-1-yl)methyl] Uridine – A Sensitive 19F NMR Sensor for the Detection of RNA Secondary Structures. The Journal of Organic Chemistry 2015, 80 (16) , 7961-7970. https://doi.org/10.1021/acs.joc.5b00973
- Lotta Granqvist and Pasi Virta . 4′-C-[(4-Trifluoromethyl-1H-1,2,3-triazol-1-yl)methyl]thymidine as a Sensitive 19F NMR Sensor for the Detection of Oligonucleotide Secondary Structures. The Journal of Organic Chemistry 2014, 79 (8) , 3529-3536. https://doi.org/10.1021/jo500326j
- Anu Kiviniemi, Merita Murtola, Petri Ingman, and Pasi Virta . Synthesis of Fluorine-Labeled Peptide Nucleic Acid Building Blocks as Sensors for the 19F NMR Spectroscopic Detection of Different Hybridization Modes. The Journal of Organic Chemistry 2013, 78 (11) , 5153-5159. https://doi.org/10.1021/jo400014y
- Kelly Phelps, Alexi Morris, and Peter A. Beal . Novel Modifications in RNA. ACS Chemical Biology 2012, 7 (1) , 100-109. https://doi.org/10.1021/cb200422t
- Jan Riedl, Radek Pohl, Lubomír Rulíšek, and Michal Hocek . Synthesis and Photophysical Properties of Biaryl-Substituted Nucleos(t)ides. Polymerase Synthesis of DNA Probes Bearing Solvatochromic and pH-Sensitive Dual Fluorescent and 19F NMR Labels. The Journal of Organic Chemistry 2012, 77 (2) , 1026-1044. https://doi.org/10.1021/jo202321g
- Anu Kiviniemi and Pasi Virta . Synthesis of Aminoglycoside-3′-Conjugates of 2′-O-Methyl Oligoribonucleotides and Their Invasion to a 19F labeled HIV-1 TAR Model. Bioconjugate Chemistry 2011, 22 (8) , 1559-1566. https://doi.org/10.1021/bc200101r
- Roba Moumné, Morgane Pasco, Elise Prost, Thomas Lecourt, Laurent Micouin, and Carine Tisné. Fluorinated Diaminocyclopentanes as Chiral Sensitive NMR Probes of RNA Structure. Journal of the American Chemical Society 2010, 132 (38) , 13111-13113. https://doi.org/10.1021/ja1037885
- Anu Kiviniemi and Pasi Virta. Characterization of RNA Invasion by 19F NMR Spectroscopy. Journal of the American Chemical Society 2010, 132 (25) , 8560-8562. https://doi.org/10.1021/ja1014629
- (Associate Editor). Nucleic Acids: Expanding the Structural and Functional Horizons. Journal of the American Chemical Society 2009, 131 (11) , 3791-3793. https://doi.org/10.1021/ja9012485
- Alexey Sudakov, Bozana Knezic, Martin Hengesbach, Boris Fürtig, Elke Stirnal, Harald Schwalbe. Site‐Specific Labeling of RNAs with Modified and 19 F‐Labeled Nucleotides by Chemo‐Enzymatic Synthesis. Chemistry – A European Journal 2023, 29 (25) https://doi.org/10.1002/chem.202203368
- Maja Marušič, Maria Toplishek, Janez Plavec. NMR of RNA - Structure and interactions. Current Opinion in Structural Biology 2023, 79 , 102532. https://doi.org/10.1016/j.sbi.2023.102532
- Jiayu Jiang, Lixian Wen, Hongshuang Wang, Xiaoguang Chen, Yanchuan Zhao, Xiaohui Wang. Detection and identification of amphetamine-type stimulants and analogs via recognition-enabled “chromatographic” 19F NMR. Journal of Fluorine Chemistry 2023, 266 , 110085. https://doi.org/10.1016/j.jfluchem.2023.110085
- Harshita Shet, Rajesh Sahu, Yogesh S. Sanghvi, Anant R. Kapdi. Strategies for the Synthesis of Fluorinated Nucleosides, Nucleotides and Oligonucleotides. The Chemical Record 2022, 22 (9) https://doi.org/10.1002/tcr.202200066
- Vanessa de Jesus, Jacklyn Schmid, Boris Fürtig. Binding of 30S Ribosome Induces Single-stranded Conformation Within and Downstream of the Expression Platform in a Translational Riboswitch. Journal of Molecular Biology 2022, 434 (18) , 167668. https://doi.org/10.1016/j.jmb.2022.167668
- Shingo Hirashima, Hiroshi Sugiyama, Soyoung Park. Characterization of 2‐Fluoro‐2’‐deoxyadenosine in Duplex, G‐Quadruplex and i‐Motif. ChemBioChem 2022, 23 (12) https://doi.org/10.1002/cbic.202200222
- Diana Gimenez, Aoife Phelan, Cormac D Murphy, Steven L Cobb. 19 F NMR as a tool in chemical biology. Beilstein Journal of Organic Chemistry 2021, 17 , 293-318. https://doi.org/10.3762/bjoc.17.28
- Jodi Kraus, Sucharita Sarkar, Caitlin M. Quinn, Tatyana Polenova. Solid-state NMR spectroscopy of microcrystalline proteins. 2021, 81-151. https://doi.org/10.1016/bs.arnmr.2020.10.002
- Maximilian Himmelstoß, Kevin Erharter, Eva Renard, Eric Ennifar, Christoph Kreutz, Ronald Micura. 2′- O -Trifluoromethylated RNA – a powerful modification for RNA chemistry and NMR spectroscopy. Chemical Science 2020, 11 (41) , 11322-11330. https://doi.org/10.1039/D0SC04520A
- Felix Nußbaumer, Raphael Plangger, Manuel Roeck, Christoph Kreutz. Aromatic 19 F– 13 C TROSY—[ 19 F, 13 C]‐Pyrimidine Labeling for NMR Spectroscopy of RNA. Angewandte Chemie 2020, 132 (39) , 17210-17217. https://doi.org/10.1002/ange.202006577
- Felix Nußbaumer, Raphael Plangger, Manuel Roeck, Christoph Kreutz. Aromatic 19 F– 13 C TROSY—[ 19 F, 13 C]‐Pyrimidine Labeling for NMR Spectroscopy of RNA. Angewandte Chemie International Edition 2020, 59 (39) , 17062-17069. https://doi.org/10.1002/anie.202006577
- William H. Gmeiner. Chemistry of Fluorinated Pyrimidines in the Era of Personalized Medicine. Molecules 2020, 25 (15) , 3438. https://doi.org/10.3390/molecules25153438
- Robbin Schnieders, Sara Keyhani, Harald Schwalbe, Boris Fürtig. More than Proton Detection—New Avenues for NMR Spectroscopy of RNA. Chemistry – A European Journal 2020, 26 (1) , 102-113. https://doi.org/10.1002/chem.201903355
- Jennifer Frommer, Sabine Müller. Changed reactivity of secondary hydroxy groups in C8-modified adenosine – lessons learned from silylation. Beilstein Journal of Organic Chemistry 2020, 16 , 2854-2861. https://doi.org/10.3762/bjoc.16.234
- Hong-Liang Bao, Hong-shan Liu, Yan Xu. Hybrid-type and two-tetrad antiparallel telomere DNA G-quadruplex structures in living human cells. Nucleic Acids Research 2019, 47 (10) , 4940-4947. https://doi.org/10.1093/nar/gkz276
- Takumi Ishizuka, Hong-Liang Bao, Yan Xu. 19F NMR Spectroscopy for the Analysis of DNA G-Quadruplex Structures Using 19F-Labeled Nucleobase. 2019, 407-433. https://doi.org/10.1007/978-1-4939-9666-7_26
- Carl Philipp Rosenau, Benson J. Jelier, Alvar D. Gossert, Antonio Togni. Fluor-NMR-Spektroskopie rekalibriert. Angewandte Chemie 2018, 130 (30) , 9672-9677. https://doi.org/10.1002/ange.201802620
- Carl Philipp Rosenau, Benson J. Jelier, Alvar D. Gossert, Antonio Togni. Exposing the Origins of Irreproducibility in Fluorine NMR Spectroscopy. Angewandte Chemie International Edition 2018, 57 (30) , 9528-9533. https://doi.org/10.1002/anie.201802620
- Ilektra-Chara Giassa, Jan Rynes, Tomas Fessl, Silvie Foldynova-Trantirkova, Lukas Trantirek. Advances in the cellular structural biology of nucleic acids. FEBS Letters 2018, 592 (12) , 1997-2011. https://doi.org/10.1002/1873-3468.13054
- Hong-Liang Bao, Yan Xu. Investigation of higher-order RNA G-quadruplex structures in vitro and in living cells by 19F NMR spectroscopy. Nature Protocols 2018, 13 (4) , 652-665. https://doi.org/10.1038/nprot.2017.156
- Eirini Fotopoulou, Luca Ronconi. Application of Heteronuclear NMR Spectroscopy to Bioinorganic and Medicinal Chemistry ☆. 2018https://doi.org/10.1016/B978-0-12-409547-2.10947-3
- Hong‐Liang Bao, Takumi Ishizuka, Ayaka Iwanami, Takanori Oyoshi, Yan Xu. A Simple and Sensitive 19 F NMR Approach for Studying the Interaction of RNA G‐Quadruplex with Ligand Molecule and Protein. ChemistrySelect 2017, 2 (15) , 4170-4175. https://doi.org/10.1002/slct.201700711
- Hong-Liang Bao, Takumi Ishizuka, Takashi Sakamoto, Kenzo Fujimoto, Tamayo Uechi, Naoya Kenmochi, Yan Xu. Characterization of human telomere RNA G-quadruplex structures in vitro and in living cells using 19F NMR spectroscopy. Nucleic Acids Research 2017, 45 (9) , 5501-5511. https://doi.org/10.1093/nar/gkx109
- Takumi Ishizuka, Pei-Yan Zhao, Hong-Liang Bao, Yan Xu. A multi-functional guanine derivative for studying the DNA G-quadruplex structure. The Analyst 2017, 142 (21) , 4083-4088. https://doi.org/10.1039/C7AN00941K
- Fengmin Guo, Qiang Li, Chuanzheng Zhou. Synthesis and biological applications of fluoro-modified nucleic acids. Organic & Biomolecular Chemistry 2017, 15 (45) , 9552-9565. https://doi.org/10.1039/C7OB02094E
- Qiulong Zhang, Huanhuan Lv, Lili Wang, Man Chen, Fangfei Li, Chao Liang, Yuanyuan Yu, Feng Jiang, Aiping Lu, Ge Zhang. Recent Methods for Purification and Structure Determination of Oligonucleotides. International Journal of Molecular Sciences 2016, 17 (12) , 2134. https://doi.org/10.3390/ijms17122134
- Lotta Granqvist, Pasi Virta. Characterization of G-Quadruplex/Hairpin Transitions of RNAs by 19 F NMR Spectroscopy. Chemistry - A European Journal 2016, 22 (43) , 15360-15372. https://doi.org/10.1002/chem.201602898
- F. Sochor, R. Silvers, D. Müller, C. Richter, B. Fürtig, H. Schwalbe. 19F-labeling of the adenine H2-site to study large RNAs by NMR spectroscopy. Journal of Biomolecular NMR 2016, 64 (1) , 63-74. https://doi.org/10.1007/s10858-015-0006-9
- Robert G. Brinson, Jennifer T. Miller, Jason D. Kahn, Stuart F.J. Le Grice, John P. Marino. Applying Thymine Isostere 2,4-Difluoro-5-Methylbenzene as a NMR Assignment Tool and Probe of Homopyrimidine/Homopurine Tract Structural Dynamics. 2016, 89-110. https://doi.org/10.1016/bs.mie.2015.05.009
- Shigetaka Nakamura, Kenzo Fujimoto. Photo-cross-linking using trifluorothymidine and 3-cyanovinylcarbazole induced a large shifted 19 F MR signal. Chemical Communications 2015, 51 (59) , 11765-11768. https://doi.org/10.1039/C5CC02972D
- L. Iannazzo, E. Benedetti, M. Catala, M. Etheve-Quelquejeu, C. Tisné, L. Micouin. Monitoring of reversible boronic acid–diol interactions by fluorine NMR spectroscopy in aqueous media. Organic & Biomolecular Chemistry 2015, 13 (33) , 8817-8821. https://doi.org/10.1039/C5OB01362C
- Felix Spenkuch, Gerald Hinze, Stefanie Kellner, Christoph Kreutz, Ronald Micura, Thomas Basché, Mark Helm. Dye label interference with RNA modification reveals 5-fluorouridine as non-covalent inhibitor. Nucleic Acids Research 2014, 42 (20) , 12735-12745. https://doi.org/10.1093/nar/gku908
- Alejandro Gimenez Molina, Amit M Jabgunde, Pasi Virta, Harri Lönnberg. Solution phase synthesis of short oligoribonucleotides on a precipitative tetrapodal support. Beilstein Journal of Organic Chemistry 2014, 10 , 2279-2285. https://doi.org/10.3762/bjoc.10.237
- Kazuhito Tanabe, Takuya Tsuda, Takeo Ito, Sei-ichi Nishimoto. Probing DNA Mismatched and Bulged Structures by Using 19 F NMR Spectroscopy and Oligodeoxynucleotides with an 19 F-Labeled Nucleobase. Chemistry - A European Journal 2013, 19 (45) , 15133-15140. https://doi.org/10.1002/chem.201302770
- Han Chen, Stéphane Viel, Fabio Ziarelli, Ling Peng. 19F NMR: a valuable tool for studying biological events. Chemical Society Reviews 2013, 42 (20) , 7971. https://doi.org/10.1039/c3cs60129c
- Katja Fauster, Christoph Kreutz, Ronald Micura. 2′-SCF 3 Uridine-A Powerful Label for Probing Structure and Function of RNA by 19 F NMR Spectroscopy. Angewandte Chemie 2012, 124 (52) , 13257-13261. https://doi.org/10.1002/ange.201207128
- Katja Fauster, Christoph Kreutz, Ronald Micura. 2′-SCF 3 Uridine-A Powerful Label for Probing Structure and Function of RNA by 19 F NMR Spectroscopy. Angewandte Chemie International Edition 2012, 51 (52) , 13080-13084. https://doi.org/10.1002/anie.201207128
- Nerea Martín-Pintado, Maryam Yahyaee-Anzahaee, Ramón Campos-Olivas, Anne M. Noronha, Christopher J. Wilds, Masad J. Damha, Carlos González. The solution structure of double helical arabino nucleic acids (ANA and 2′F-ANA): effect of arabinoses in duplex-hairpin interconversion. Nucleic Acids Research 2012, 40 (18) , 9329-9339. https://doi.org/10.1093/nar/gks672
- Tobias A. Plöger, Günter von Kiedrowski. Improved Large-Scale Liquid-Phase Synthesis and High-Temperature NMR Characterization of Short (F-)PNAs. Helvetica Chimica Acta 2011, 94 (11) , 1952-1980. https://doi.org/10.1002/hlca.201100243
- Célia S. Bonnet, Pascal H. Fries. Paramagnetic Relaxation Enhancements in Acetate and Its Fluorine Derivatives Interacting with Gd3+: Complex Formation, Structure, and Transmetallation. ChemPhysChem 2010, 11 (16) , 3474-3484. https://doi.org/10.1002/cphc.201000448
- Gui-Fang Wang, Conggang Li , Gary J. Pielak. Probing the Micelle-Bound Aggregation-Prone State of α-Synuclein with 19F NMR Spectroscopy. ChemBioChem 2010, 11 (14) , 1993-1996. https://doi.org/10.1002/cbic.201000405
- A. Singh, R. P. Sharma, T. Aree, P. Venugopalan. Weak C-H…F-C interactions in carboxylate anion binding: Synthesis, spectroscopic and X-ray structural studies of [Co(phen)2CO3]2 (C7H3O2FCl)Cl·11H2O and [Co(phen)2CO3](C7H3NO4Cl)·6H2O. Journal of Chemical Sciences 2010, 122 (5) , 739-750. https://doi.org/10.1007/s12039-010-0062-3
- Kazuhito Tanabe, Masaaki Sugiura, Sei-ichi Nishimoto. Monitoring of duplex and triplex formation by 19F NMR using oligodeoxynucleotides possessing 5-fluorodeoxyuridine unit as 19F signal transmitter. Bioorganic & Medicinal Chemistry 2010, 18 (18) , 6690-6694. https://doi.org/10.1016/j.bmc.2010.07.066
- Ulrike Rieder, Christoph Kreutz, Ronald Micura. Folding of a transcriptionally acting PreQ 1 riboswitch. Proceedings of the National Academy of Sciences 2010, 107 (24) , 10804-10809. https://doi.org/10.1073/pnas.0914925107
- Claudia Höbartner, Falk Wachowius. Chemical Synthesis of Modified RNA. 2010, 1-37. https://doi.org/10.1002/9780470664001.ch1
- David Loakes. Nucleotides and Nucleic Acids; Oligo- and Polynucleotides. 2010, 144-237. https://doi.org/10.1039/9781849730839-00144
- Falk Wachowius, Claudia Höbartner. Chemical RNA Modifications for Studies of RNA Structure and Dynamics. ChemBioChem 2010, 11 (4) , 469-480. https://doi.org/10.1002/cbic.200900697
- H. Shaghaghi, H. Ebrahimi, M. Tafazzoli, M. Jalali-Heravi. A survey of wave function effects on theoretical calculation of gas phase 19F NMR chemical shifts using factorial design. Journal of Fluorine Chemistry 2010, 131 (1) , 47-52. https://doi.org/10.1016/j.jfluchem.2009.09.020
- Barbara Puffer, Christoph Kreutz, Ulrike Rieder, Marc-Olivier Ebert, Robert Konrat, Ronald Micura. 5-Fluoro pyrimidines: labels to probe DNA and RNA secondary structures by 1D 19 F NMR spectroscopy. Nucleic Acids Research 2009, 37 (22) , 7728-7740. https://doi.org/10.1093/nar/gkp862
- William C. Pomerantz, Erik B. Hadley, Charles G. Fry, Samuel H. Gellman. In Situ Monitoring of Backbone Thioester Exchange by 19 F NMR. ChemBioChem 2009, 10 (13) , 2177-2181. https://doi.org/10.1002/cbic.200900380
- Bastian Holzberger, Andreas Marx. Enzymatic synthesis of perfluoroalkylated DNA. Bioorganic & Medicinal Chemistry 2009, 17 (10) , 3653-3658. https://doi.org/10.1016/j.bmc.2009.03.063