Conformational studies on analogues of the invertebrate peptide pyroGlu-Asp-Pro-Phe-Leu-Arg-Phe-NH2 using 1H NMR

Abstract

The peptide pQDPFLR Famide is one of several closely related heptapeptides found in invertebrates, including molluscs. Electrophysiological findings and ligand binding studies have both suggested that these heptapeptides probably interact with receptors distinct from those that are activated b y the related tetrapeptide FMRFamide (also found in the same group of invertebrates), despite the fact that some synthetic N-terminally extended analogues of the latter show marked tetrapeptidelike activity. We have carried out structural studies, using 1and 2-dimensional 'H NMR, o n pQDPFLRFamide and some synthetic analogues in which Asp-2 was replaced by Asn and Pro-3 by either Aib (E-amino isobutyric acid) or by Gly. The results are consistent with the suggestion that pQDPFLRFamide can adopt a bent conformation, which might form the basis of the selectivity of this and related heptapeptides.Two types of FMRFamide-related peptides (Farps), containing either four or seven amino acids have been found in several groups of invertebrates, including molluscs.'q2 These peptides are thought to participate in a range of neuroregulatory functions. In the land snail Helix aspersa, the peptides include FXRFamide (X = M or L) and XDPFLRFamide (X = pQ, S or N).3,4 Cloning of the gene that codes for the heptapeptides in this mollusc has revealed the presence of other, closely related heptapeptide sequence^.^ Electrophysiological studies in this Paper 4/00302K