Cyclic enkephalin analogues with exceptional potency and selectivity for δ-opioid receptors

Victor J. Hruby, Hubert Bartosz-Bechowski, Peg Davis, Jirina Slaninova, Teresa Zalewska, Dagmar Stropova, Frank Porreca, Henry I. Yamamura

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34 Scopus citations

Abstract

Superpotent and highly δ-opioid receptor selective cyclic peptides of the general formula H-Tyr-c[D-Pen-Gly-Phe(p-X)-Pen]-Phe-OH (where X = hydrogen or halogen) have been synthesized. In the binding assays the most selective and most potent compound is the p-bromophenyl-alanine-4 analogue (IC50 value = 0.19 nM, selectivity ratio = 21 000 for δ vs μ). In the GPI and MVD bioassays the most selective and most potent analogue is the p- fluoro-substituted analogue Tyr-[D-Pen-Gly-Phe(p-F)-Pen]-Phe-OH. In the MVD assay it has an exceptionally low IC50 value of 0.016 nM and a δ vs μ selectivity ratio of 45 000.

Original languageEnglish (US)
Pages (from-to)3957-3962
Number of pages6
JournalJournal of Medicinal Chemistry
Volume40
Issue number24
DOIs
StatePublished - Dec 12 1997

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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    Hruby, V. J., Bartosz-Bechowski, H., Davis, P., Slaninova, J., Zalewska, T., Stropova, D., Porreca, F., & Yamamura, H. I. (1997). Cyclic enkephalin analogues with exceptional potency and selectivity for δ-opioid receptors. Journal of Medicinal Chemistry, 40(24), 3957-3962. https://doi.org/10.1021/jm9704762