C12 Helices in Long Hybrid (αγ)n Peptides Composed Entirely of Unconstrained Residues with Proteinogenic Side Chains

Abstract

Unconstrained γ(4) amino acid residues derived by homologation of proteinogenic amino acids facilitate helical folding in hybrid (αγ)n sequences. The C12 helical conformation for the decapeptide, Boc-[Leu-γ(4)(R)Val]5-OMe, is established in crystals by X-ray diffraction. A regular C12 helix is demonstrated by NMR studies of the 18 residue peptide, Boc-[Leu-γ(4)(R)Val]9-OMe, and a designed 16 residue (αγ)n peptide, incorporating variable side chains. Unconstrained (αγ)n peptides show an unexpectedly high propensity for helical folding in long polypeptide sequences.