Crystallographic characterization of the α ,γ C12 helix in hybrid peptide sequences

Abstract

The solid-state conformations of two αγ hybrid peptides Boc-[Aib-γ4(R)Ile]4-OMe 1 and Boc-[Aib-γ4(R)Ile]5-OMe 2 are described. Peptides 1 and 2 adopt C12-helical conformations in crystals. The structure of octapeptide 1 is stabilized by six intramolecular 4 → 1 hydrogen bonds, forming 12 atom C12 motifs. The structure of peptide 2 reveals the formation of eight successive C12 hydrogen-bonded turns. Average backbone dihedral angles for αγ C12 helices are peptide 1, Aib; φ (°) = −57.2 ± 0.8, ψ (°) = −44.5 ± 4.7; γ4(R)Ile; φ (°) = −127.3 ± 7.3, θ1 (°) = 58.5 ± 12.1, θ2 (°) = 67.6 ± 10.1, ψ (°) = −126.2 ± 16.1; peptide 2, Aib; φ (°) = −58.8 ± 5.1, ψ (°) = −40.3 ± 5.5; ψ4(R)Ile; φ (°) = −123.9 ± 2.7, θ1 (°) = 53.3 θ 4.9, θ 2 (°) = 61.2 ± 1.6, ψ (°) = −121.8 ± 5.1. The tendency of γ4-substituted residues to adopt gauche–gauche conformations about the Cα–Cβ and Cβ–Cγ bonds facilitates helical folding. The αγ C12 helix is a backbone expanded analog of α peptide 310 helix. The hydrogen bond parameters for α peptide 310 and α-helices are compared with those for αγ hybrid C12 helix.