Selective and Wash-Resistant Fluorescent Dihydrocodeinone Derivatives Allow Single-Molecule Imaging of mu-Opioid Receptor Dimerization

Gentzsch C, Seier K, Drakopoulos A, Jobin ML, Lanoiselee Y, Koszegi Z, Maurel D, Sounier R, Hübner H, Gmeiner P, Granier S, Calebiro D, Decker M (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Angewandte Chemie International Edition Wiley

DOI: 10.1002/anie.201912683

Abstract

mu-Opioid receptors (mu-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 mu-ORs produce specific effects in living cells. We developed new fluorescent ligands based on the mu-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 mu-ORs on the surface of living cells at physiological expression levels. Our results reveal a high heterogeneity in the diffusion of mu-ORs, with a relevant immobile fraction. Using a pair of fluorescent ligands of different color, we provide evidence that mu-ORs interact with each other to form short-lived homodimers on the plasma membrane. This approach provides a new strategy to investigate mu-OR pharmacology at single-molecule level.

Authors with CRIS profile

Harald Hübner Lehrstuhl für Pharmazeutische Chemie Peter Gmeiner Lehrstuhl für Pharmazeutische Chemie

Involved external institutions

Julius-Maximilians-Universität Würzburg DE Germany (DE) University of Birmingham GB United Kingdom (GB) University of Montpellier / Université Montpellier FR France (FR)

How to cite

APA:

Gentzsch, C., Seier, K., Drakopoulos, A., Jobin, M.-L., Lanoiselee, Y., Koszegi, Z.,... Decker, M. (2020). Selective and Wash-Resistant Fluorescent Dihydrocodeinone Derivatives Allow Single-Molecule Imaging of mu-Opioid Receptor Dimerization. Angewandte Chemie International Edition. https://doi.org/10.1002/anie.201912683

MLA:

Gentzsch, Christian, et al. "Selective and Wash-Resistant Fluorescent Dihydrocodeinone Derivatives Allow Single-Molecule Imaging of mu-Opioid Receptor Dimerization." Angewandte Chemie International Edition (2020).

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