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

Sarott, Roman C; Westphal, Matthias V; Pfaff, Patrick; Korn, Claudia; Sykes, David A; Gazzi, Thais; Brennecke, Benjamin; Atz, Kenneth; Weise, Marie; Mostinski, Yelena; Hompluem, Pattarin; Koers, Eline; Miljuš, Tamara; Roth, Nicolas J; Asmelash, Hermon; Vong, Man C; Piovesan, Jacopo; Guba, Wolfgang; Rufer, Arne C; Kusznir, Eric A; ... (2020). Development of High-Specificity Fluorescent Probes to Enable Cannabinoid Type 2 Receptor Studies in Living Cells. Journal of the American Chemical Society, 142(40), pp. 16953-16964. American Chemical Society 10.1021/jacs.0c05587

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine

UniBE Contributor:

Mandhair, Harpreet Kaur and Gertsch, Jürg

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0002-7863

Publisher:

American Chemical Society

Language:

English

Submitter:

Barbara Järmann-Bangerter

Date Deposited:

18 Jan 2021 11:51

Last Modified:

18 Jan 2021 11:51

Publisher DOI:

10.1021/jacs.0c05587

PubMed ID:

32902974

BORIS DOI:

10.48350/150892

URI:

https://boris.unibe.ch/id/eprint/150892

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