Bimodal use of chiral α‐Trifluoromethylalanine in Aib Foldamers: study of the position impact towards the helical screw‐sense preference

Introduction of a chiral α-trifluoromethylalanine residue into Aib oligomers proved its effectiveness as a bimodal moiety, acting both as controller and ¹⁹F NMR reporter of the helical screw-sense preference. By varying its position along the chain and the nature of the C-terminal capping, our study revealed the stereoelectronic properties of the CF₃ group enabling the control of the helical conformation.

Abstract

Oligomers 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.

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