Helical secondary structures in 2:1 and 1:2 α/γ-peptide foldamers

Oligomers containing both alpha- and gamma-amino acid residues in a 1:1 alternating pattern have recently been shown by several research groups to adopt helical secondary structures. We have begun to explore the folding behavior of oligomers with different alpha-residue/gamma-residue backbone patterns. Previously we reported that the gamma-amino acids bearing a cyclohexyl constraint at the C-beta-C-gamma bond and a variable side chain at C-alpha strongly promote a helical conformation containing 12-atom C=O(i)center dot center dot center dot H-N(i+3) hydrogen bonds for 1:1 alpha:gamma backbones. Here we report synthesis and crystallographic analysis of 2:1 and 1:2 alpha/gamma-peptides that adopt C=O(i)center dot center dot center dot H-N(i+3) hydrogen-bonded helical conformations. (C) 2012 Elsevier Ltd. All rights reserved.