Synthetic peptides related to the dermorphins. I. Synthesis and biological activities of the shorter homologues and of analogues of the heptapeptides.

Dermorphins are potent opiate-like peptides isolated from the skin of some species of frogs. They are characterized by the presence of a D-amino acid residue, which is crucial for bioactivity. A number of analogues were prepared in order to evaluate the structure-activity relationships. The syntheses were accomplished either by conventional or solid-phase procedures. In vitro assays included both guinea pig ileum (GPI) and mouse vas deferens (MVD) preparations. Central analgesic (tail-flick and hot plate tests) and cataleptic activities were determined in the rat by intracerebroventricular route. The potency of dermorphin (H- Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2) in the different tests was: GPI: IC50 = 3.3 nM; MVD: IC50 = 29 nM; hot plate: ED50 = 13.3 pmol/rat; tail-flick: ED50 = 23 pmol/rat; catalepsy: ED50 = 130 pmol/rat.