Structural characterization of folded and extended conformations in peptides containing γ amino acids with proteinogenic side chains: crystal structures of γn, (αγ)n and γγδγ sequences

Abstract

The crystal structures of nine peptides containing γ4Val and γ4Leu are described. The short sequences Boc-[γ4(R)Val]2-OMe 1, Boc-[γ4(R)Val]3-NHMe 2 and Boc-γ4(S)Val-γ4(R)Val-OMe 3 adopt extended apolar, sheet like structures. The tetrapeptide Boc-[γ4(R)Val]4-OMe 4 adopts an extended conformation, in contrast to the folded C14 helical structure determined previously for Boc-[γ4(R)Leu]4-OMe. The hybrid αγ sequence Boc-[Ala-γ4(R)Leu]2-OMe 5 adopts an S-shaped structure devoid of intramolecular hydrogen bonds, with both α residues adopting local helical conformations. In sharp contrast, the tetrapeptides Boc-[Aib-γ4(S)Leu]2-OMe 6 and Boc-[Leu-γ4(R)Leu]2-OMe 7 adopt folded structures stabilized by two successive C12 hydrogen bonds. γ4Val residues have also been incorporated into the strand segments of a crystalline octapeptide, Boc-Leu-γ4(R)Val-Val-DPro-Gly-Leu-γ4(R)Val-Val-OMe 8. The γγδγ tetrapeptide containing γ4Val and δ5Leu residues adopts an extended sheet like structure. The hydrogen bonding pattern at γ residues corresponds to an apolar sheet, while a polar sheet is observed at the lone δ residue. The transition between folded and extended structures at γ residues involves a change of the torsion angle from the gauche to the trans conformation about the Cβ–Cα bond.