Conformations of dehydrophenylalanine containing peptides: nmr studies of an acyclic hexapeptide with two Δ^z-Phe residues

Abstract

The conformation of an acyclic dehydrophenylalanine (Δ^z-Phe) containing hexapeptide, Boc-Phe-Δ^z-Phe-Val-Phe-Δ^z-Phe-Val-OMe, has been investigated in CDCl₃ and (CD₃)₂SO by 270-MHz ¹H-NMR. Studies of NH group solvent accessibility and observation of interresidue nuclear Overhauser effects (NOEs) suggest a significant solvent-dependent conformational variability. In CDCl₃, a population of folded helical conformations is supported by the inaccessibility to solvent of the NH groups of residues 3-6 and the detection of several N_iH ↔ N_i+1H NOEs. Evidence is also obtained for conformational heterogeneity from the detection of some C^α _iH ↔ N_i+1H NOEs characteristic of extended strands. In (CD₃)₂SO, the peptide largely favors an extended conformation, characterized by five solvent-exposed NH groups and successive C^α_iH ↔ N_i+1 H NOEs for the L-residues and C^β_iH ↔ N_i+1H NOEs for the Δ^z-Phe residues. The results suggest that Δ^z-Phe residues do not provide compelling conformational constraints.