Synthesis and biological activity of carboxyl terminally extended dermorphins.
Dermorphinoyl(DMR)-glycine, DMR-sarcosine and DMR-glycyl-arginine have been prepared in order to examine the effect of C-terminal extension of dermorphin (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2) on opioid activity. On GPI preparation the addition of Gly, Sar, or Gly-Arg to the carboxyl terminus of dermorphinoic acid was detrimental to mu activity: dermorphinoyl-derivatives, in fact, retain only 5-20% of dermorphin potency. Following intracerebroventricular administration (tail-flick test), whereas the analgesic activities of compounds showed the trend dermorphin greater than DMR-Sar greater than DMR-Gly-Arg greater than DMR-Gly greater than morphine, the nonapeptide displayed highest activity after subcutaneous injection in mice: DMR-Gly-Arg was 2.5 and 10 times more potent than dermorphin and morphine, respectively.
D000595:Amino Acid Sequence; D000818:Animals; D006168:Guinea Pigs; D009119:Muscle Contraction / Q000187:drug effects; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D018847:Opioid Peptides; D013329:Structure-Activity Relationship
D009842:Oligopeptides; D018847:Opioid Peptides; C030058:dermorphin