Stabilization of unusual structures in peptides using alpha,beta-dehydrophenylalanine: crystal and solution structures of Boc-Pro-DeltaPhe-Val-DeltaPhe-Ala-OMe and Boc-Pro-DeltaPhe-Gly-DeltaPhe-Ala-OMe

Biopolymers. 2006;84(3):298-309. doi: 10.1002/bip.20439.

Abstract

The structures of two dehydropentapeptides, Boc-Pro-DeltaPhe-Val-DeltaPhe-Ala-OMe (I) and Boc-Pro-DeltaPhe-Gly-DeltaPhe-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 beta-bend structure, characterized by two partially overlapping type II beta-bends and absence of a second 1 <-- 4 (N4--H . . . O1') intramolecular hydrogen bond. This is in contrast to the generally observed 3(10)-helical conformation in peptides with DeltaPhe 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(gamma)HVal(3) 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 3(10)-helix. Both peptides I and II are classical examples of stabilization of unusual structures in oligopeptides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acids / chemistry
  • Circular Dichroism
  • Crystallization
  • Crystallography, X-Ray
  • Hydrogen Bonding
  • Models, Molecular
  • Nuclear Magnetic Resonance, Biomolecular
  • Oligopeptides / analysis*
  • Oligopeptides / chemistry
  • Phenylalanine / analogs & derivatives*
  • Phenylalanine / chemistry
  • Protein Conformation
  • Protein Structure, Secondary
  • Lösungen

Substances

  • Amino Acids
  • Oligopeptides
  • Lösungen
  • Phenylalanine
  • phenyldehydroalanine