Detection of cannabinoid receptor type 2 in native cells and zebrafish with a highly potent, cell-permeable fluorescent probe
| Autor: | Thais Gazzi, Benjamin Brennecke, Kenneth Atz, Claudia Korn, David Sykes, Gabriel Forn-Cuni, Patrick Pfaff, Roman C. Sarott, Matthias V. Westphal, Yelena Mostinski, Leonard Mach, Malgorzata Wasinska-Kalwa, Marie Weise, Bradley L. Hoare, Tamara Miljuš, Maira Mexi, Nicolas Roth, Eline J. Koers, Wolfgang Guba, André Alker, Arne C. Rufer, Eric A. Kusznir, Sylwia Huber, Catarina Raposo, Elisabeth A. Zirwes, Anja Osterwald, Anto Pavlovic, Svenja Moes, Jennifer Beck, Matthias Nettekoven, Irene Benito-Cuesta, Teresa Grande, Faye Drawnel, Gabriella Widmer, Daniela Holzer, Tom van der Wel, Harpreet Mandhair, Michael Honer, Jürgen Fingerle, Jörg Scheffel, Johannes Broichhagen, Klaus Gawrisch, Julián Romero, Cecilia J. Hillard, Zoltan V. Varga, Mario van der Stelt, Pal Pacher, Jürg Gertsch, Christoph Ullmer, Peter J. McCormick, Sergio Oddi, Herman P. Spaink, Mauro Maccarrone, Dmitry B. Veprintsev, Erick M. Carreira, Uwe Grether, Marc Nazaré |
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| Přispěvatelé: | Publica |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Gazzi, Thais; Brennecke, Benjamin; Atz, Kenneth; Korn, Claudia; Sykes, David; Forn-Cuni, Gabriel; Pfaff, Patrick; Sarott, Roman C; Westphal, Matthias V; Mostinski, Yelena; Mach, Leonard; Wasinska-Kalwa, Malgorzata; Weise, Marie; Hoare, Bradley L; Miljuš, Tamara; Mexi, Maira; Roth, Nicolas; Koers, Eline J; Guba, Wolfgang; Alker, André; ... (2022). Detection of cannabinoid receptor type 2 in native cells and zebrafish with a highly potent, cell-permeable fluorescent probe. Chemical Science, 13(19), pp. 5539-5545. The Royal Society of Chemistry 10.1039/d1sc06659e Chemical Science, 13(19), 5539-5545 Chemical Science |
| Popis: | Despite its essential role in the (patho)physiology of several diseases, CB2R tissue expression profiles and signaling mechanisms are not yet fully understood. We report the development of a highly potent, fluorescent CB2R agonist probe employing structure-based reverse design. It commences with a highly potent, preclinically validated ligand, which is conjugated to a silicon-rhodamine fluorophore, enabling cell permeability. The probe is the first to preserve interspecies affinity and selectivity for both mouse and human CB2R. Extensive cross-validation (FACS, TR-FRET and confocal microscopy) set the stage for CB2R detection in endogenously expressing living cells along with zebrafish larvae. Together, these findings will benefit clinical translatability of CB2R based drugs. |
| Databáze: | OpenAIRE |
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