Conformations of dehydrophenylalanine containing peptides: NMR studies on three tripeptides with a central dehydrophenylalanyl residue

Abstract

Three tripeptides containing a central Z-dehydrophenylalanine residue (Δ^z-Phe), Boc-L-Phe-Δ^z-Phe-X-OMe (X = L-Val 1, L-Leu 2 and X = L-Ala 3) have been synthesized and their solution conformations investigated by 270 MHz ¹H NMR spectroscopy. In all three peptides, conformations involving the X residue NH in an intramolecular hydrogen bond were favoured in CDCl₃ solutions. Studies of the nuclear Overhauser effect (NOE) provided support for a Type II β turn conformation in these peptides with Phe and Δ^z-Phe occupying the i + 1 and i + 2 positions, respectively. Significantly different conformations lacking any intramolecular hydrogen bonds were observed for peptide 1 in (CD₃)₂SO. NOE results were consistent with a significant population of molecules having semi-extended conformations (∅ > 100°) at the Δ^z-Phe residue.