Structural studies of model peptides containing β-, γ and δ-amino acids

Abstract

The crystal structures of five model peptides Piv-Pro-Gly-NHMe (1), Piv-Pro-βGly-NHMe (2), Piv-Pro-βGly-OMe (3), Piv-Pro-δAva-OMe (4) and Boc-Pro-γAbu-OH (5) are described (Piv: pivaloyl; NHMe: N-methylamide; βGly: β-glycine; OMe: O-methyl ester; δAva: δ-aminovaleric acid; γAbu: γ-aminobutyric acid). A comparison of the structures of peptides 1 and 2 illustrates the dramatic consequences upon backbone homologation in short sequences. 1 adopts a type II β-turn conformation in the solid state, while in 2, the molecule adopts an open conformation with the β-residue being fully extended. Piv-Pro-βGly-OMe (3), which differs from 2 by replacement of the C-terminal NH group by an O-atom, adopts an almost identical molecular conformation and packing arrangement in the solid state. In peptide 4, the observed conformation resembles that determined for 2 and 3, with the δAva residue being fully extended. In peptide 5, the molecule undergoes a chain reversal, revealing a β-turn mimetic structure stabilized by a C-H···O hydrogen bond.