Selective and Wash‐Resistant Fluorescent Dihydrocodeinone Derivatives Allow Single‐Molecule Imaging of μ‐Opioid Receptor Dimerization. (7th January 2020)

• Record Type: Journal Article
• Authors: Gentzsch, Christian; Seier, Kerstin; Drakopoulos, Antonios; Jobin, Marie‐Lise; Lanoiselée, Yann; Koszegi, Zsombor; Maurel, Damien; Sounier, Rémy; Hübner, Harald; Gmeiner, Peter; Granier, Sébastien; Calebiro, Davide; Decker, Michael
• Is Part Of: Angewandte Chemie. Volume 132:Number 15(2020)
• Page Start: 6014
• Page End: 6020
• Publication Date: 2020-01-07
• Subjects: Fluoreszenzsonden -- G-Protein-gekoppelte Rezeptoren -- Homodimerisierung -- Opioidliganden -- Einzelmolekülmikroskopie; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201912683
• Languages: English
• ISSNs: 0044-8249

Abstract

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. Abstract : Ein Paar fluoreszierender, selektiver μ‐Opioidrezeptorliganden wurde synthetisiert und in Einzelmolekülmikroskopie‐Experimenten eingesetzt. Nach ihrer pharmakologischen Charakterisierung wurden die Liganden verwendet, um das Diffusionsverhalten und die Homodimerisierung von Wildtyp μ‐Opioidrezeptoren auf der Oberfläche lebender Zellen zu untersuchen.