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
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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.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine |
UniBE Contributor: |
Mandhair, Harpreet Kaur, Gertsch, Jürg |
Subjects: |
500 Science > 570 Life sciences; biology 600 Technology > 610 Medicine & health |
ISSN: |
2041-6520 |
Publisher: |
The Royal Society of Chemistry |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
14 Jun 2022 10:37 |
Last Modified: |
05 Dec 2022 16:20 |
Publisher DOI: |
10.1039/d1sc06659e |
PubMed ID: |
35694350 |
BORIS DOI: |
10.48350/170629 |
URI: |
https://boris.unibe.ch/id/eprint/170629 |
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