A novel opioid structure which accepts protonated as well as non-protonated nitrogen: A family of pure, delta receptor selective antagonists

A. Z. Rónai, J. Botyánszki, J. Hepp, K. Medzihradszky

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Conventional opioids including opioid peptides require an "opioid" nitrogen which exists in protonated state while interacting with the receptor. In the present paper we demonstrate that Tyr-Pro-Gly-Phe-Leu-Thr hexapeptide sequence accepts N-terminal substituents such as N-t-Boc, N-phenylacetyl and N-diphenylacetyl where the N cannot become protonated, as well as "traditional" substitutions such as N,N-diallyl, where protonation is likely under physiological conditions. The opioid peptides bearing these substituents are pure antagonists of medium affinity (Ke values in the mouse vas deferens bioassay against [Met5]-enkephalin are in the 3×10-7 - 4×10-6M range) with a high delta receptor preference (50 - 350-fold delta over mu selectivity ratios).

Original languageEnglish
Pages (from-to)1371-1378
Number of pages8
JournalLife sciences
Volume50
Issue number18
DOIs
Publication statusPublished - 1992

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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