Conformationally constrained cyclic enkephalin analogs with pronounced delta opioid receptor agonist selectivity

Henry I. Mosberg, Robin Hurst, Victor J. Hruby, James J. Galligan, Thomas F. Burks, Kelvin Gee, Henry I. Yamamura

Research output: Contribution to journalArticle

91 Scopus citations

Abstract

The enkephalin analogs, [D-Pen2, L-Cys5]- and [D-Pen2, D-Cys5]- enkephalin are cyclic compounds, conformationally constrained by virtue of their 14-membered, disulfide containing rings and by the rigidizing effect of the β,β dimethyl substituents of the penicilamine side chain. The analogs exhibit profound δ receptor specificity as assessed by their relative potencies in the guinea pig ileum (GPI) and mouse vas deferens (MVD) assays, exhibiting, respectively, 666 and 215 times higher potency in the latter assat system. By contrast, the receptor selectivities measured in rat brain binding assays in the absence of sodium were much more modest, the cyclic analogs being, respectively, 15.2 and 6.0 times more effective at displacing [3H] [D-Ala2, D-Leu5] enkephalin than [3H] naloxone. However, for binding assays performed in the presence of a sodium concentration equivalent to that used in the GPI and MVD assays, these binding selectivities increased to 167 and 49, respectively.

Original languageEnglish (US)
Pages (from-to)2565-2569
Number of pages5
JournalLife Sciences
Volume32
Issue number22
DOIs
StatePublished - May 30 1983

ASJC Scopus subject areas

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

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