Solution conformation and synthesis of a linear heptapeptide containing two dehydrophenylalanine residues separated by three L-amino acids

Abstract

A heptapeptide containing two dehydrophenylalanine residues, Boc-Gly-Δ^zPhe-Ala-Phe-Leu-Δ^zPhe-Ala-NHMe (Boc = t-butoxycarbonyl) has been synthesised and its solution conformation investigated using 500 MHz ¹H NMR and IR spectroscopy. ¹H NMR studies of the solvent accessibility of NH resonances and observation of successive N_i,H ↔ N_i+1H nuclear Overhauser effects (NOEs) suggest the presence of a significant population of folded, helical structures in CDCl₃. A 5→1 intramolecular hydrogen bonding pattern provides evidence in favour of an α-helix conformation. In (CD₃)₂SO, although the peptide largely favours the helical conformation, observation of a few C_i^αH ↔ N_i+1H NOEs gives an indication of some conformational heterogeneity. IR studies in chloroform have provided supporting evidence in favour of these conclusions. Dehydrophenylalanine residues may be of potential use in designing peptides with preferred secondary structures.