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 C^β–C^α bond.