Chemistry, an Asian journal | 2019
Ambidextrous α,γ-Hybrid Peptide Foldamers.
Abstract
Molecular chirality is ubiquitous in nature.\xa0 The natural biopolymers, proteins and DNA, preferred right-handed helical bias due to the inherent stereochemistry of monomer building blocks. Here, we are reporting a rare co-existence of left and right-handed helical conformations and helix terminating property at the C-terminus within a single molecule of α,γ-hybrid peptide foldamers composed of achiral Aib and 3,3-dimethyl substituted γ-amino acid (Adb). The molecular level left- and right-handed helical screw sense of α,γ-hybrid peptides are representing a macroscopic tendril perversion. The pronounced helix terminating behaviour of C-terminal Adb residues was further explored to design helix-Schellman loop mimetics and to study their conformations in solution and single crystals. The stereochemical constraints of dialkyl substitutions on γ-amino acids have showed a marked impact on the folding behaviour of α,γ-hybrid peptides.