Synthesis and pharmacological activity of partially modified retro-inverso dermorphin tetrapeptides.
We studied the effect of partial retro-inverso modification of selected peptide bonds of N-terminal tetrapeptide analogues of dermorphin (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2). Among the 14 compounds synthesized and tested for opioid activity, some tetrapeptides have the C-terminus carrying different amide moieties; retromodifications concern the Phe-Gly bond (Ia-f) and/or the C-terminal carboxamide function (IIIa-d, IIa-d). All pseudotetrapeptide derivatives showed opioid activity in vitro and in vivo. The most potent compounds (II) 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 intracerebral or subcutaneous administration.
D000818:Animals; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D051379:Mice; D009294:Narcotics / Q000138:chemical synthesis* / Q000494:pharmacology; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D018847:Opioid Peptides; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D009294:Narcotics; D009842:Oligopeptides; D018847:Opioid Peptides; C030058:dermorphin