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

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18 Citations (Scopus)


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
Issue number18
Publication statusPublished - 1992


ASJC Scopus subject areas

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

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