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

Christian Gentzsch, Kerstin Seier, Antonios Drakopoulos, Marie-Lise Jobin, Yann Lanoiselée, Zsombor Koszegi, Damien Maurel, Remy Sounier, Harald Hübner, Peter Gmeiner, Sebastien Granier, Davide Calebiro, Michael Decker

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4 Citations (Scopus)
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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.

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

Keywords

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

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