Conformational study of some component peptides of pentagastrin

Abstract

The proton n.m.r. spectra of Asp, Phe, Asp-Phe-NH₂, Met-Asp-Phe-NH₂, Trp-Met-Asp-Phe-NH₂, and Boc-βAla-Trp-Met-Asp-Phe-NH₂ have been studied in aqueous and dimethyl sulphoxide solutions. From an analysis of the ¹H spectra of the Asp and Phe C(α)H·C(β)H₂ side-chains the vicinal coupling constants were obtained and used to calculate the rotational populations. There are no significant differences in the Phe side-chain rotamer populations between the tripeptide Met-Asp-Phe-NH₂ and gastrin pentapeptide βAla-Trp-Met-Asp-Phe-NH₂, but the Asp residue shows some small changes. The presence of only small ring-current shielding contributions to the Phe aromatic protons from the aromatic ring in Trp can be taken to indicate that the aromatic rings are well separated (>5 Å) in the most populated conformers of gastrin pentapeptide in aqueous solution. For dimethyl sulphoxide solutions, NH doublets could be observed for the peptides studied; the large values of the vicinal J_NC coupling constants for Met, Asp, and Phe in the tetrapeptide Trp-Met-Asp-Phe-NH₂ are shown to be consistent with the most populated conformations, having a ϕ angle of ca. –95°, from considerations of potential energy diagrams and the Bystrov-modified Karplus curve which relates dihedral angles to vicinal coupling constants.