Bimodal Use of Chiral α‐Trifluoromethylalanine in Aib Foldamers: Study of the Position Impact Towards the Helical Screw‐Sense Preference

Abstract

AbstractOligomers of the achiral α‐aminoisobutyric acid (Aib) adopt a 310 helical conformation in which the screw‐sense preference can be controlled by a single chiral residue. The use of the fluorinated residue α‐Trifluoromethylalanine (α‐TfmAla) revealed a unique way to both induce and measure the screw‐sense preference of such oligomers acting as 19F NMR probe. This work proposes a systematic study of the effect of this fluorinated chiral inducer on the helical screw‐sense preference of poly‐Aib oligomers. The impact of the position of the fluorinated residue into pentamers (N‐terminal, central or C‐terminal) as well as the nature of the C‐terminal capping of the peptides was thoroughly studied in light of complete structural analysis. A deeper understanding of the fluorine effect was achieved confirming the unique ability of α‐TfmAla as a helical screw‐sense controller.