Tuned-affinity bivalent ligands for the characterization of opioid receptor heteromers

Jessica H. Harvey, Darcie H. Long, Pamela M. England, Jennifer Whistler

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Opioid receptors, including the μ- and δ-opioid receptors (MOR and DOR), are important targets for the treatment of pain. Although there is mounting evidence that these receptors form heteromers, the functional role of the MOR/DOR heteromer remains unresolved. We have designed and synthesized bivalent ligands as tools to elucidate the functional role of the MOR/DOR heteromer. Our ligands (L2 and L4) are comprised of a compound with low affinity at the DOR tethered to a compound with high affinity at the MOR, with the goal of producing ligands with "tuned affinity" at MOR/DOR heteromers as compared to DOR homomers. Here, we show that both L2 and L4 demonstrate enhanced affinity at MOR/DOR heteromers as compared to DOR homomers, thereby providing unique pharmacological tools to dissect the role of the MOR/DOR heteromer in pain.

Original languageEnglish (US)
Pages (from-to)640-644
Number of pages5
JournalACS Medicinal Chemistry Letters
Volume3
Issue number8
DOIs
StatePublished - Aug 9 2012
Externally publishedYes

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Keywords

  • bivalent ligand
  • chronic pain
  • heteromers
  • opioid receptors

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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