Novel [D-Arg2]dermorphin(1-4) analogs with mu-opioid receptor antagonist activity

Chem Pharm Bull (Tokyo). 2002 Oct;50(10):1401-3. doi: 10.1248/cpb.50.1401.

Abstract

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.

MeSH terms

  • Animals
  • Brain / metabolism
  • Dose-Response Relationship, Drug
  • Guinea Pigs
  • Male
  • Narcotic Antagonists / chemistry*
  • Narcotic Antagonists / metabolism*
  • Oligopeptides / chemistry*
  • Oligopeptides / metabolism*
  • Rats
  • Receptors, Opioid, mu / antagonists & inhibitors*
  • Receptors, Opioid, mu / metabolism

Substances

  • Narcotic Antagonists
  • Oligopeptides
  • Receptors, Opioid, mu
  • tyrosyl-alanyl-phenylalanyl-glycine