[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

26 Citations (Scopus)

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

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Dynorphins
Narcotic Antagonists
Opioid Receptors
Adenylyl Cyclases
Assays
dynorphin A (1-11)-amide
2,3-diaminopropionic acid
dynorphin (1-13)

All Science Journal Classification (ASJC) codes

  • Organic Chemistry

Cite this

[Nα-benzylTyr1,cyclo(D-Asp5,Dap 8)]-dynorphin A-(1-11)NH2 cyclized in the "address" domain is a novel κ-opioid receptor antagonist. / Patkar, Kshitij A.; Yan, Xiuzhen; Murray, Thomas F.; Aldrich, Jane V.

In: Journal of Medicinal Chemistry, Vol. 48, No. 14, 14.07.2005, p. 4500-4503.

Research output: Contribution to journalArticle

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AU - Aldrich, Jane V.

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