Conformations of dehydrophenylalanine containing peptides nuclear overhauser effect study of two acyclic tetrapeptides

Abstract

Two isomeric, acyclic tetrapeptides containing a Z-dehydrophenylalanine residue (Δ^z-Phe) at position 2 or 3, Boc-Leu-Ala-Δ^z-Phe-Leu-OMe (1) and Boc-Leu-Δ^z-Phe-Ala-Leu-OMe (2), have been synthesized and their solution conformations investigated by 270MHz ¹H n.m.r. spectroscopy. In peptide 1 the Leu(4) NH group appears to be partially shielded from solvent, while in peptide 2 both Ala(3) and Leu(4) NH groups show limited solvent accessibility. Extensive difference nuclear Overhauser effect (n.O.e.) studies establish the occurrence of several diagnostic inter-residue n.O.e.s (Cα_jH ⇔ N_i+1H and N_iH ⇔ N_i+1H) between backbone protons. The simultaneous observation of "mutually exclusive" n.O.e.s suggests the presence of multiple solution conformations for both peptides. In peptide 1 the n.O.e. data are consistent with a dynamic equilibrium between an -Ala-Δ^z-Phe- Type II β-turn structure and a second species with Δ^z-Phe adopting a partially extended conformation with ψ values of ± 100° to ± 150°. In peptide 2 the results are compatible with an equilibrium between a highly folded consecutive β-turn structure for the -Leu-Δ^z-Phe-Ala- segment and an almost completely extended conformation.