Stabilization of unusual structures in peptides using α,β-dehydrophenylalanine: crystal and solution structures of Boc-Pro-ΔPhe-Val-ΔPhe-Ala-OMe and Boc-Pro-ΔPhe-Gly-ΔPhe-Ala-OMe

Abstract

The structures of two dehydropentapeptides, Boc-Pro-ΔPhe-Val-ΔPhe-Ala-OMe (I) and Boc-Pro-ΔPhe-Gly-ΔPhe-Ala-OMe (II) (Boc: t-butoxycarbonyl), have been determined by nuclear magnetic resonance (NMR), circular dichroism (CD), and X-ray crystallographic studies. The peptide I assumes a S-shaped flat β-bend structure, characterized by two partially overlapping type II β-bends and absence of a second 1 <-4 (N4-H ^... O1') intramolecular hydrogen bond. This is in contrast to the generally observed 3₁₀-helical conformation in peptides with ΔPhe at alternate positions. This report describes the novel conformation assumed by peptide I and compares it with that of the conserved tip of the V3 loop of the HIV-1 envelope glycoprotein gp120 (sequence, G:P319 to F:P324, PDB code 1ACY). The tip of the V3 loop also assumes a S-shaped conformation with Arg:P322, making an intramolecular side-chain-backbone interaction with the carbonyl oxygen of Gly:P319. Interestingly, in peptide I, C^γHVal³ makes a similar side-chain-backbone C-H ^... O hydrogen bond with the carbonyl oxygen of the Boc group. The observed overall similarity indicates the possible use of the peptide as a viral antagonist or synthetic antigen. Peptide II adopts a unique turn followed by a 3₁₀-helix. Both peptides I and II are classical examples of stabilization of unusual structures in oligopeptides.