Selective and wash‐resistant fluorescent dihydrocodeinone derivatives allow single‐molecule imaging of μ‐opioid receptor dimerization

Research output: Contribution to journalArticle

Authors

  • Christian Gentzsch
  • Kerstin Seier
  • Antonios Drakopoulos
  • Marie-Lise Jobin
  • Damien Maurel
  • Remy Sounier
  • Harald Hübner
  • Peter Gmeiner
  • Sebastien Granier
  • Michael Decker

Colleges, School and Institutes

Abstract

μ-Opioid receptors (μ-ORs) play a critical role in the modulation of pain and mediate the effects of the most powerful analgesic drugs. Despite extensive efforts, it remains insufficiently understood how μ-ORs produce specific effects in living cells. We developed new fluorescent ligands based on the μ-OR antagonist E-p-nitrocinnamoylamino-dihydrocodeinone (CACO), that display high affinity, long residence time and pronounced selectivity. Using these ligands, we achieved single-molecule imaging of μ-ORs on the surface of living cells at physiological expression levels. Our results reveal a high heterogeneity in the diffusion of μ-ORs, with a relevant immobile fraction. Using a pair of fluorescent ligands of different color, we provide evidence that μ-ORs interact with each other to form short-lived homodimers on the plasma membrane. This approach provides a new strategy to investigate μ-OR pharmacology at single-molecule level.

Details

Original languageEnglish
JournalAngewandte Chemie (International Edition)
Early online date6 Dec 2019
Publication statusE-pub ahead of print - 6 Dec 2019

Keywords

  • mu Opioid Receptor, GPCR, morphinan, homodimers, florescence