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

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Selective and wash‐resistant fluorescent dihydrocodeinone derivatives allow single‐molecule imaging of μ‐opioid receptor dimerization. / Gentzsch, Christian; Seier, Kerstin; Drakopoulos, Antonios; Jobin, Marie-Lise; Lanoiselée, Yann; Koszegi, Zsombor; Maurel, Damien; Sounier, Remy; Hübner, Harald; Gmeiner, Peter; Granier, Sebastien; Calebiro, Davide; Decker, Michael.

In: Angewandte Chemie (International Edition) , 06.12.2019.

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Gentzsch, Christian ; Seier, Kerstin ; Drakopoulos, Antonios ; Jobin, Marie-Lise ; Lanoiselée, Yann ; Koszegi, Zsombor ; Maurel, Damien ; Sounier, Remy ; Hübner, Harald ; Gmeiner, Peter ; Granier, Sebastien ; Calebiro, Davide ; Decker, Michael. / Selective and wash‐resistant fluorescent dihydrocodeinone derivatives allow single‐molecule imaging of μ‐opioid receptor dimerization. In: Angewandte Chemie (International Edition) . 2019.

Bibtex

@article{4c47e84d2276411b933632ef2f4e661a,
title = "Selective and wash‐resistant fluorescent dihydrocodeinone derivatives allow single‐molecule imaging of μ‐opioid receptor dimerization",
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.",
keywords = "mu Opioid Receptor, GPCR, morphinan, homodimers, florescence",
author = "Christian Gentzsch and Kerstin Seier and Antonios Drakopoulos and Marie-Lise Jobin and Yann Lanoisel{\'e}e and Zsombor Koszegi and Damien Maurel and Remy Sounier and Harald H{\"u}bner and Peter Gmeiner and Sebastien Granier and Davide Calebiro and Michael Decker",
year = "2019",
month = dec
day = "6",
doi = "10.1002/anie.201912683",
language = "English",
journal = "Angewandte Chemie (International Edition) ",
issn = "1433-7851",
publisher = "Wiley-VCH Verlag",

}

RIS

TY - JOUR

T1 - Selective and wash‐resistant fluorescent dihydrocodeinone derivatives allow single‐molecule imaging of μ‐opioid receptor dimerization

AU - Gentzsch, Christian

AU - Seier, Kerstin

AU - Drakopoulos, Antonios

AU - Jobin, Marie-Lise

AU - Lanoiselée, Yann

AU - Koszegi, Zsombor

AU - Maurel, Damien

AU - Sounier, Remy

AU - Hübner, Harald

AU - Gmeiner, Peter

AU - Granier, Sebastien

AU - Calebiro, Davide

AU - Decker, Michael

PY - 2019/12/6

Y1 - 2019/12/6

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.

AB - 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 - mu Opioid Receptor

KW - GPCR

KW - morphinan

KW - homodimers

KW - florescence

U2 - 10.1002/anie.201912683

DO - 10.1002/anie.201912683

M3 - Article

C2 - 31808251

JO - Angewandte Chemie (International Edition)

JF - Angewandte Chemie (International Edition)

SN - 1433-7851

ER -