Novel [D-Arg2]dermorphin(1-4) analogs with mu-opioid receptor antagonist activity.
Ten Tyr-D-Arg-Phe-betaAla-NH(2) (YRFB) analogs in which specific amino acid side chains are shifted to the N(alpha)-position were synthesized, and the binding to these analogs to the mu receptor and their in vitro biological properties were evaluated. Some analogs in which a N,N-bis(p-hydroxybenzyl)-Gly residue was substituted for Tyr(1) exhibited mu receptor antagonist activities (pA(2)) between 5.3 and 6.1. Of these analogs, [N,N-bis(p-hydroxybenzyl)-Gly(1)]YRFB was found to be the most potent specific antagonist for the mu-opioid receptor.
Ambo
Akihiro
A
Tohoku Pharmaceutical University, Sendai, Japan.
Terashima
Takanori
T
Sasaki
Yusuke
Y
D000818:Animals; D001921:Brain / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D008297:Male; D009292:Narcotic Antagonists / Q000737:chemistry* / Q000378:metabolism*; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism*; D051381:Rats; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors* / Q000378:metabolism
D009292:Narcotic Antagonists; D009842:Oligopeptides; D017450:Receptors, Opioid, mu; C053416:tyrosyl-alanyl-phenylalanyl-glycine