Stereochemical matching determines both helix type and handedness in α/γ-peptides with a cyclic-constrained γ-amino acid

Abstract

The folding preferences of α/γ-peptides containing a bespoke chiral cyclobutane-constrained γ-amino acid have been examined in a low-polarity solvent by quantum chemical calculations. With (S)-alanine, the preferred conformation is a right-handed 12/10 helix, whereas with (R)-alanine a left-handed 12 helical architecture is promoted. Experimental evidence for this dichotomy was obtained by detailed analysis of the IR amide I and II absorption bands and their assignments with assistance from theoretical simulations.