Crystallographic characterization of the alpha,gamma C-12 helix in hybrid peptide sequences

The solid-state conformations of two alpha gamma hybrid peptides Boc-Aib-gamma(4)(R)Ile](4)-OMe 1 and Boc-Aib-gamma(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 alpha gamma C-12 helices are peptide 1, Aib; phi (degrees) = -57.2 +/- 0.8, psi (degrees) = -44.5 +/- 4.7; gamma(4)(R)Ile; phi (degrees) = -127.3 +/- 7.3, theta(1) (degrees) = 58.5 +/- 12.1, theta(2) (degrees)= 67.6 +/- 10.1, psi (degrees) = -126.2 +/- 16.1; peptide 2, Aib; phi (degrees) = -58.8 +/- 5.1, psi (degrees) = -40.3 +/- 5.5; psi(4)(R)Ile; phi (degrees) = -123.9 +/- 2.7, theta(1) (degrees) = 53.3 theta 4.9, theta(2) (degrees) = 61.2 +/- 1.6, psi (degrees) = -121.8 +/- 5.1. The tendency of gamma(4)-substituted residues to adopt gauche-gauche conformations about the C-alpha-C-beta and C-beta-C-gamma bonds facilitates helical folding. The alpha gamma C-12 helix is a backbone expanded analog of alpha peptide 3(10) helix. The hydrogen bond parameters for alpha peptide 3(10) and alpha-helices are compared with those for alpha gamma hybrid C-12 helix. Copyright (C) 2016 European Peptide Society and John Wiley & Sons