TY  - JOUR
A1  - Christian, Gentzsch
A1  - Seier, Kerstin
A1  - Drakopoulos, Antonios
A1  - Jobin, Marie-Lise
A1  - Lanoiselée, Yann
A1  - Koszegi, Zsombor
A1  - Maurel, Damien
A1  - Sounier, Rémy
A1  - Hübner, Harald
A1  - Gmeiner, Peter
A1  - Granier, Sébastien
A1  - Calebiro, Davide
A1  - Decker, Michael
T1  - Selective and Wash‐Resistant Fluorescent Dihydrocodeinone Derivatives Allow Single‐Molecule Imaging of μ‐Opioid Receptor Dimerization
JF  - Angewandte Chemie International Edition
N2  - 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.
KW  - single-molecule microscopy
KW  - fluorescent probes
KW  - G-protein coupled receptor
KW  - homodimerization
KW  - opioid ligands
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-212398
VL  - 59
IS  - 15
ER  -