[Nα-benzylTyr1,cyclo(D-Asp5,Dap 8)]-dynorphin A-(1-11)NH2 cyclized in the "address" domain is a novel κ-opioid receptor antagonist

Kshitij A. Patkar, Xiuzhen Yan, Thomas F. Murray, Jane V. Aldrich

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

The cyclic dynorphin A analogue [Nα-benzylTyr1, cyclo(D-Asp5,Dap8)]dynorphin A-(1-11)NH2 (Dap = 2,3-diaminopropionic acid) exhibits nanomolar affinity (30 nM) and high selectivity (Ki ratio (κ/μ/δ) = 1/194/330) for κ-opioid receptors. This analogue antagonizes dynorphin A-(1-13)NH 2 at κ-opioid receptors in the adenylyl cyclase assay (K B = 84 nM). This is the first dynorphin A-based antagonist with modifications in the C-terminal "address" domain that alter efficacy and thus represents a novel selective κ-opioid receptor antagonist.

Original languageEnglish (US)
Pages (from-to)4500-4503
Number of pages4
JournalJournal of Medicinal Chemistry
Volume48
Issue number14
DOIs
StatePublished - Jul 14 2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

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