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

• Published in: Journal of peptide science 2016-08, Vol.22 (8), p.504-510
• Main Authors: Reddy, Madhusudana M. B., Basuroy, Krishnayan, Aravinda, Subrayashastry, Balaram, Padmanabhan
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; C12 helix; Carrier Proteins - chemistry; Crystallography, X-Ray; Humans; hybrid peptide sequences; Hydrogen Bonding; Models, Molecular; Peptides - chemical synthesis; Peptides - chemistry; polypeptides; Protein Structure, Secondary
• ISSN: 1075-2617; 1099-1387
• DOI: 10.1002/psc.2896

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. Copyright © 2016 European Peptide Society and John Wiley & Sons.