Cyclic enkephalin analogs with exceptional potency at peripheral δ opioid receptors

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

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18 Scopus citations

Abstract

A series of super potent and δ-opioid-receptor-selective cyclic hexapeptides of the general formula H-Tyr-D-Pen-Gly-Phe(p-X)-Cys-Phe-OH (where X is hydrogen or halogen) has been synthesized. The unsubstituted hexapeptide H-Tyr-D-Pen-Gly-Phe-Cys-Phe-OH (HB-P2, [Phe6]DPLCE) has extremely high potency at peripheral δ opioid receptors (IC50 value in the MVD assay is 0.016 nM) and in bioassays is the most selective compound in this series. The introduction of halogens in the phenyl ring of phenylalanine at position 4 led to significant changes in the selectivity and affinities at peripheral and central opioid receptors. In the binding studies, the most potent compound is the p-fluoro analog, whereas the most selective analog is the p-iodo-substituted peptide.

Original languageEnglish (US)
Pages (from-to)146-150
Number of pages5
JournalJournal of Medicinal Chemistry
Volume37
Issue number1
Publication statusPublished - 1994

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ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Bartosz-Bechowski, H., Davis, P., Zalewska, T., Slaninova, J., Porreca, F., Yamamura, H. I., & Hruby, V. J. (1994). Cyclic enkephalin analogs with exceptional potency at peripheral δ opioid receptors. Journal of Medicinal Chemistry, 37(1), 146-150.