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

Oligomers containing both α- and γ-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 α-residue/γ-residue backbone patterns. Previously we reported that the γ-amino acids bearing a cyclohexyl constraint at the Cβ–Cγ bond and a variable side chain at Cα strongly promote a helical conformation containing 12-atom Cdouble bond; length as m-dashO(i)⋯H–N(i+3) hydrogen bonds for 1:1 α:γ backbones. Here we report synthesis and crystallographic analysis of 2:1 and 1:2 α/γ-peptides that adopt Cdouble bond; length as m-dashO(i)⋯H–N(i+3) hydrogen-bonded helical conformations.