[D-Pen2,D-Pen5]enkephalin Analogues with Increased Affinity and Selectivity for δ Opioid Receptors

Geza Toth, Victor J. Hruby, Thomas H. Kramer, Richard Knapp, George Lui, Peg Davis, Thomas F. Burks, Henry I. Yamamura

Research output: Contribution to journalArticlepeer-review

83 Scopus citations


The conformationaUy restricted, cyclic disulfide-containing enkephalin analogue [D-Pen2,D-Pen5]enkephalin (DPDPE) was modified by halogenation (F, Cl, Br, I) of the phenylalanine-4 residue in the para position. The potency and selectivity of these analogues for the δ opioid receptor was greater than that of the parent peptide. The analogues possessed greater potency and affinity for the δ receptors than DPDPE in the mouse vas deferens assay and in radioreceptor assays (against [3H]DPDPE), respectively. [p-ClPhe4]DPDPE was the most selective in the radioligand binding assays(IC50(δ) = 574), being about 5-fold more δ opioid receptor selective than DPDPE in this assay, whereas [p-IPhe4]DPDPE was the most selective in the classical bioassay systems using the mouse vas deferens and guinea pig ileum assays (IC50GPI)/IC50MVD) = 17374), making it nearly 9-fold more selective than DPDPE in direct comparisons using the same assay conditions.

Original languageEnglish (US)
Pages (from-to)249-253
Number of pages5
JournalJournal of Medicinal Chemistry
Issue number1
StatePublished - Jan 1990
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery


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