Conformationally Rigid Trifluoromethyl-Substituted α-Amino Acid Designed for Peptide Structure Analysis by Solid-State ~(19)F NMR Spectroscopy

摘要

The incorporation of specifically fluorine-labeled L--amino acids (FAAs) into polypeptides is a prerequisite for analyzing them by 19F NMR spectroscopy. The advantages of observing this isotope arise from its high sensitivity, the absence of biological background signals, its wide range of chemical shifts, and strong dipolar interactions.[1], [2] An FAA is usually incorporated into a peptide by solid-phase peptide synthesis (SPPS), though some other methods have also been developed.[1], [3] In most NMR applications the FAAs simply serve to probe qualitative changes in the local environment.[1] Only recently, FAAs have been incorporated into membrane-bound peptides to determine explicit structural parameters in terms of orientational constraints and/or interatomic distances by solid-state 19F NMR spectrosopy.[4], [5] These solid-state NMR studies are particularly informative about membrane-active peptides, as they can reveal their conformation, alignment, and dynamic behavior in a lipid bilayer under quasi-native conditions.[4] However, only a limited number of FAAs are applicable to this approach, as they must meet certain structural requirements.[5] All of the compounds (1-6) used in the past face certain drawbacks in terms of either their structural interpretation and/or their chemical incorporation into peptides.