A photochromic agonist for μ-opioid receptors

Matthias Schönberger, Dirk Trauner

Research output: Contribution to journalArticle

Abstract

Opioid receptors (ORs) are widely distributed in the brain, the spinal cord, and the digestive tract and play an important role in nociception. All known ORs are G-protein-coupled receptors (GPCRs) of family A. Another well-known member of this family, rhodopsin, is activated by light through the cis/trans isomerization of a covalently bound chromophore, retinal. We now show how an OR can be combined with a synthetic azobenzene photoswitch to gain light sensitivity. Our work extends the reach of photopharmacology and outlines a general strategy for converting Family A GPCRs, which account for the majority of drug targets, into photoreceptors. Lighting up the opioid receptor: Photofentanyl-2 is a photochromic version of the well-known analgesic fentanyl. It is a potent agonist in the dark (or when illuminated with blue light) and loses activity when irradiated with UV light. It can be used to optically control the μ-opioid receptor, converting a G-protein-coupled receptor (GPCR) into a photoreceptor.

Original languageEnglish (US)
Pages (from-to)3264-3267
Number of pages4
JournalAngewandte Chemie - International Edition
Volume53
Issue number12
DOIs
StatePublished - Mar 17 2014

Keywords

  • azobenzenes
  • fentanyl
  • opioid receptors
  • photopharmacology
  • photoswitches

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

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