- Treffer 1 von 1
Selective and Wash‐Resistant Fluorescent Dihydrocodeinone Derivatives Allow Single‐Molecule Imaging of μ‐Opioid Receptor Dimerization
Zitieren Sie bitte immer diese URN: urn:nbn:de:bvb:20-opus-212398
- 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 atμ‐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.…
Autor(en): | Gentzsch Christian, Kerstin Seier, Antonios Drakopoulos, Marie-Lise Jobin, Yann Lanoiselée, Zsombor Koszegi, Damien Maurel, Rémy Sounier, Harald Hübner, Peter Gmeiner, Sébastien Granier, Davide Calebiro, Michael Decker |
---|---|
URN: | urn:nbn:de:bvb:20-opus-212398 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Institut für Pharmakologie und Toxikologie |
Fakultät für Chemie und Pharmazie / Institut für Pharmazie und Lebensmittelchemie | |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | Angewandte Chemie International Edition |
Erscheinungsjahr: | 2020 |
Band / Jahrgang: | 59 |
Heft / Ausgabe: | 15 |
Seitenangabe: | 5958–5964 |
Originalveröffentlichung / Quelle: | Angewandte Chemie International Edition, 2020, 59(15), 5958–5964. DOI: 10.1002/anie.201912683 |
DOI: | https://doi.org/10.1002/anie.201912683 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften |
Freie Schlagwort(e): | G-protein coupled receptor; fluorescent probes; homodimerization; opioid ligands; single-molecule microscopy |
Datum der Freischaltung: | 06.10.2020 |
Lizenz (Deutsch): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |