Design, synthesis and validation of fluorine-containing analogues of natural amino acids as 19F-NMR labels used in structural studies of antimicrobial, cell-penetrating and other membrane-active peptides
Over ~15 years, the collaboration with scientists from Karlsruhe Institute of Technology produced a “toolbox” of the fluorine-containing labels. These CF3- and F- substituted analogues of natural low-polar, polar and charged amino acids were incorporated in membrane-active peptides, and then the fluorine nucleus was used as a reporter to get structural constraints for the peptides embedded in model and natural lipid bilayers. The CF3-substituted bicyclopentane-derived amino acid CF3-Bpg is now used by several groups for peptide structural studies, and might be regarded as a “working horse” in this area.
More than a dozen of different membrane-active peptides were studied by this method, among them are antimicrobial, cell-penetrating, fibril-forming and other membrane-active peptides.
Komarov I. V., Afonin S., Ulrich A. S. 19F-Labeled amino acids for NMR structure analysis of membrane-bound peptides. Fluorine in Life Sciences: Pharmaceuticals, Medicinal Diagnostics, and Agrochemicals. – Academic Press, 2019. P. 349-395.
A.N. Tkachenko, P.K. Mykhailiuk, S. Afonin, D.S. Radchenko, V.S. Kubyshkin, A.S. Ulrich, I.V. Komarov. A 19F NMR Label To Substitute Polar Amino Acids in Peptides: A CF3-Substituted Analogue of Serine and Threonine. Angew. Chem. Int. Ed. 2013, 52, 1486–1489.