Crystallographic characterization of the α ,γ C 12 helix in hybrid peptide sequences

The solid‐state conformations of two α γ hybrid peptides Boc‐[Aib‐γ 4 ( R )Ile] 4 ‐OMe 1 and Boc‐[Aib‐γ 4 ( R )Ile] 5 ‐OMe 2 are described. Peptides 1 and 2 adopt C 12 ‐helical conformations in crystals. The structure of octapeptide 1 is stabilized by six intramolecular 4 → 1 hydrogen bonds, forming 12 atom C 12 motifs. The structure of peptide 2 reveals the formation of eight successive C 12 hydrogen‐bonded turns. Average backbone dihedral angles for α γ C 12 helices are peptide 1 , Aib; φ (°) = −57.2 ± 0.8, ψ (°) = −44.5 ± 4.7; γ 4 ( R )Ile; φ (°) = −127.3 ± 7.3, θ 1 (°) = 58.5 ± 12.1, θ 2 (°) = 67.6 ± 10.1, ψ (°) = −126.2 ± 16.1; peptide 2 , Aib; φ (°) = −58.8 ± 5.1, ψ (°) = −40.3 ± 5.5; ψ 4 ( R )Ile; φ (°) = −123.9 ± 2.7, θ 1 (°) = 53.3 θ 4.9, θ 2 (°) = 61.2 ± 1.6, ψ (°) = −121.8 ± 5.1. The tendency of γ 4 ‐substituted residues to adopt gauche–gauche conformations about the C α –C β and C β –C γ bonds facilitates helical folding. The α γ C 12 helix is a backbone expanded analog of α peptide 3 10 helix. The hydrogen bond parameters for α peptide 3 10 and α ‐helices are compared with those for α γ hybrid C 12 helix. Copyright © 2016 European Peptide Society and John Wiley & Sons.