Back
Full-text
Journal article

Development of High-Specificity Fluorescent Probes to Enable Cannabinoid Type 2 Receptor Studies in Living Cells.

  • Sarott RC Laboratorium für Organische Chemie, Eidgenössische Technische Hochschule Zürich, Vladimir-Prelog-Weg 3, 8093 Zürich, Switzerland.
  • Westphal MV Laboratorium für Organische Chemie, Eidgenössische Technische Hochschule Zürich, Vladimir-Prelog-Weg 3, 8093 Zürich, Switzerland.
  • Pfaff P Laboratorium für Organische Chemie, Eidgenössische Technische Hochschule Zürich, Vladimir-Prelog-Weg 3, 8093 Zürich, Switzerland.
  • Korn C Roche Pharma Research & Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland.
  • Sykes DA Faculty of Medicine & Health Sciences, University of Nottingham, Nottingham NG7 2UH, U.K.
  • Gazzi T Leibniz-Institut für Molekulare Pharmakologie FMP, Campus Berlin-Buch, 13125 Berlin, Germany.
  • Brennecke B Leibniz-Institut für Molekulare Pharmakologie FMP, Campus Berlin-Buch, 13125 Berlin, Germany.
  • Atz K Roche Pharma Research & Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland.
  • Weise M Leibniz-Institut für Molekulare Pharmakologie FMP, Campus Berlin-Buch, 13125 Berlin, Germany.
  • Mostinski Y Leibniz-Institut für Molekulare Pharmakologie FMP, Campus Berlin-Buch, 13125 Berlin, Germany.
  • Hompluem P Faculty of Medicine & Health Sciences, University of Nottingham, Nottingham NG7 2UH, U.K.
  • Koers E Faculty of Medicine & Health Sciences, University of Nottingham, Nottingham NG7 2UH, U.K.
  • Miljuš T Faculty of Medicine & Health Sciences, University of Nottingham, Nottingham NG7 2UH, U.K.
  • Roth NJ William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London EC1M 6BQ, England.
  • Asmelash H William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London EC1M 6BQ, England.
  • Vong MC Faculty of Medicine & Health Sciences, University of Nottingham, Nottingham NG7 2UH, U.K.
  • Piovesan J Faculty of Medicine & Health Sciences, University of Nottingham, Nottingham NG7 2UH, U.K.
  • Guba W Roche Pharma Research & Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland.
  • Rufer AC Roche Pharma Research & Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland.
  • Kusznir EA Roche Pharma Research & Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland.
  • Huber S Roche Pharma Research & Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland.
  • Raposo C Roche Pharma Research & Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland.
  • Zirwes EA Roche Pharma Research & Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland.
  • Osterwald A Roche Pharma Research & Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland.
  • Pavlovic A Roche Pharma Research & Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland.
  • Moes S Roche Pharma Research & Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland.
  • Beck J Roche Pharma Research & Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland.
  • Benito-Cuesta I Faculty of Experimental Sciences, Universidad Francisco de Vitoria, Pozuelo de Alarcón, 28223, Madrid, Spain.
  • Grande T Faculty of Experimental Sciences, Universidad Francisco de Vitoria, Pozuelo de Alarcón, 28223, Madrid, Spain.
  • Ruiz de Martı N Esteban S Faculty of Experimental Sciences, Universidad Francisco de Vitoria, Pozuelo de Alarcón, 28223, Madrid, Spain.
  • Yeliseev A National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland 20852, United States.
  • Drawnel F Roche Pharma Research & Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland.
  • Widmer G Roche Pharma Research & Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland.
  • Holzer D Roche Pharma Research & Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland.
  • van der Wel T Department of Molecular Physiology, Leiden Institute of Chemistry, Leiden University, 2333 CC, Leiden, The Netherlands.
  • Mandhair H Institute of Biochemistry and Molecular Medicine, University of Bern, 3012 Bern, Switzerland.
  • Yuan CY Department of Microbiology and Immunology, Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, United States.
  • Drobyski WR Department of Medicine, Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, United States.
  • Saroz Y Department of Pharmacology and Clinical Pharmacology, School of Medical Sciences, Faculty of Medical and Health Sciences, University of Auckland, 1142 Auckland, New Zealand.
  • Grimsey N Department of Pharmacology and Clinical Pharmacology, School of Medical Sciences, Faculty of Medical and Health Sciences, University of Auckland, 1142 Auckland, New Zealand.
  • Honer M Roche Pharma Research & Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland.
  • Fingerle J Roche Pharma Research & Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland.
  • Gawrisch K National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland 20852, United States.
  • Romero J Faculty of Experimental Sciences, Universidad Francisco de Vitoria, Pozuelo de Alarcón, 28223, Madrid, Spain.
  • Hillard CJ Department of Pharmacology and Clinical Pharmacology, Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, United States.
  • Varga ZV National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland 20852, United States.
  • van der Stelt M Department of Molecular Physiology, Leiden Institute of Chemistry, Leiden University, 2333 CC, Leiden, The Netherlands.
  • Pacher P National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland 20852, United States.
  • Gertsch J Institute of Biochemistry and Molecular Medicine, University of Bern, 3012 Bern, Switzerland.
  • McCormick PJ William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London EC1M 6BQ, England.
  • Ullmer C Roche Pharma Research & Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland.
  • Oddi S Faculty of Veterinary Medicine, University of Teramo, 64100 Teramo, Italy.
  • Maccarrone M European Center for Brain Research (CERC)/Santa Lucia Foundation, 00179 Rome, Italy.
  • Veprintsev DB Faculty of Medicine & Health Sciences, University of Nottingham, Nottingham NG7 2UH, U.K.
  • Nazaré M Leibniz-Institut für Molekulare Pharmakologie FMP, Campus Berlin-Buch, 13125 Berlin, Germany.
  • Grether U Roche Pharma Research & Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland.
  • Carreira EM Laboratorium für Organische Chemie, Eidgenössische Technische Hochschule Zürich, Vladimir-Prelog-Weg 3, 8093 Zürich, Switzerland.
Show more…
  • 2020-09-09
Published in:
  • Journal of the American Chemical Society. - 2020
Colloid and Surface Chemistry
Biochemistry
General Chemistry
Catalysis
English Pharmacological modulation of cannabinoid type 2 receptor (CB2R) holds promise for the treatment of numerous conditions, including inflammatory diseases, autoimmune disorders, pain, and cancer. Despite the significance of this receptor, researchers lack reliable tools to address questions concerning the expression and complex mechanism of CB2R signaling, especially in cell-type and tissue-dependent contexts. Herein, we report for the first time a versatile ligand platform for the modular design of a collection of highly specific CB2R fluorescent probes, used successfully across applications, species, and cell types. These include flow cytometry of endogenously expressing cells, real-time confocal microscopy of mouse splenocytes and human macrophages, as well as FRET-based kinetic and equilibrium binding assays. High CB2R specificity was demonstrated by competition experiments in living cells expressing CB2R at native levels. The probes were effectively applied to FACS analysis of microglial cells derived from a mouse model relevant to Alzheimer's disease.
Language
  • English
Open access status
green
Identifiers
Persistent URL
https://sonar.ch/global/documents/6176
Statistics
Document views: 47 File downloads:
  • Full-text: 0