Synthesis and pharmacological activity of partially modified retro-inverso dermorphin tetrapeptides

Abstract

The effect of partial retro-inverso modification of selected peptide bonds of N-terminal tetrapeptide analogs of dermorphin (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2) was studied. Among the 14 compounds synthesized and tested for opioid activity, some tetrapeptides have the C-terminus carrying different amide moieties; retromodifications concern the Phe.sbd.Gly bond and/or the C-terminal carboxamide function. All pseudotetrapeptide derivatives showed opioid activity in vitro and in vivo. The most potent compounds have a biological potency comparable with that of the original tetrapeptides in the guinea pig ileum preparation and in the mouse tail-flick test after intercerebral or s.c. administration.