Articles | Volume 6, issue 2
https://doi.org/10.5194/mr-6-131-2025
https://doi.org/10.5194/mr-6-131-2025
Research article
 | 
14 Jul 2025
Research article |  | 14 Jul 2025

Inter-residue through-space scalar 19F–19F couplings between CH2F groups in a protein

Yi Jiun Tan, Elwy H. Abdelkader, Iresha D. Herath, Ansis Maleckis, and Gottfried Otting

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Field: Liquid-state NMR | Topic: (Bio)Chemistry
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Cited articles

Alexeev, D., Barlow, P. N., Bury, S. M., Charrier, J.-D., Cooper, A., Hadfield, D., Jamieson, C., Kelly, S. M., Layfield, R., Mayer, R. J., McSparron, H., Price, N. C., Ramage, R., Sawyer, L., Starkmann, B. A., Uhrin, D., Wilken, J., and Young, D. W.: Synthesis, structural and biological studies of ubiquitin mutants containing (2S, 4S)-5-fluoroleucine residues strategically placed in the hydrophobic core, ChemBioChem, 4, 894–896, https://doi.org/10.1002/cbic.200300699, 2003. 
Apponyi, M. A., Ozawa, K., Dixon, N. E., and Otting, G.: Cell-free protein synthesis for analysis by NMR spectroscopy, Methods Mol. Biol., 426, 257–268, https://doi.org/10.1007/978-1-60327-058-8_16, 2008. 
August, R. A., Khan, J. A., Moody, C. M., and Young, D. W.: Stereospecific synthesis of (2S,4R)-[5,5,5-2H3]leucine, J. Chem. Soc.-Perk. T. 1, 1, 507–514, https://doi.org/10.1039/p19960000507, 1996. 
Braunschweiler, L. and Ernst, R. R.: Coherence transfer by isotropic mixing – application to proton correlation spectroscopy, J. Magn. Reson., 53, 512–528, https://doi.org/10.1016/0022-2364(83)90226-3, 1983. 
Charrier, J.-D., Hadfield, D. S., Hitchcock, P. B., and Young, D. W.: Synthesis of (2S,4S)- and (2S,4R)-5-fluoroleucine and (2S,4S)-[5,5-2H2]-5-fluoroleucine, Org. Biomol. Chem., 2, 474–482, https://doi.org/10.1039/b314933a, 2004. 
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Short summary
A protein is produced where a single amino acid type is substituted globally by a fluorinated analogue. Through-space fluorine–fluorine contacts are observed by 19F NMR (nuclear magnetic resonance) spectroscopy. Substitution of methyl groups by CH2F groups yields outstanding spectral resolution with minimal structural perturbation of the protein. Our work identifies the γ-gauche effect as the main reason for the spectral dispersion.
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