PUBLICATION
Detection of cannabinoid receptor type 2 in native cells and zebrafish with a highly potent, cell-permeable fluorescent probe
- Authors
- Gazzi, T., Brennecke, B., Atz, K., Korn, C., Sykes, D., Forn-Cuni, G., Pfaff, P., Sarott, R.C., Westphal, M.V., Mostinski, Y., Mach, L., Wasinska-Kalwa, M., Weise, M., Hoare, B.L., Miljuš, T., Mexi, M., Roth, N., Koers, E.J., Guba, W., Alker, A., Rufer, A.C., Kusznir, E.A., Huber, S., Raposo, C., Zirwes, E.A., Osterwald, A., Pavlovic, A., Moes, S., Beck, J., Nettekoven, M., Benito-Cuesta, I., Grande, T., Drawnel, F., Widmer, G., Holzer, D., van der Wel, T., Mandhair, H., Honer, M., Fingerle, J., Scheffel, J., Broichhagen, J., Gawrisch, K., Romero, J., Hillard, C.J., Varga, Z.V., van der Stelt, M., Pacher, P., Gertsch, J., Ullmer, C., McCormick, P.J., Oddi, S., Spaink, H.P., Maccarrone, M., Veprintsev, D.B., Carreira, E.M., Grether, U., Nazaré, M.
- ID
- ZDB-PUB-220614-10
- Date
- 2022
- Source
- Chemical science 13: 5539-5545 (Journal)
- Registered Authors
- Spaink, Herman P.
- Keywords
- none
- MeSH Terms
- none
- PubMed
- 35694350 Full text @ Chem Sci
Citation
Gazzi, T., Brennecke, B., Atz, K., Korn, C., Sykes, D., Forn-Cuni, G., Pfaff, P., Sarott, R.C., Westphal, M.V., Mostinski, Y., Mach, L., Wasinska-Kalwa, M., Weise, M., Hoare, B.L., Miljuš, T., Mexi, M., Roth, N., Koers, E.J., Guba, W., Alker, A., Rufer, A.C., Kusznir, E.A., Huber, S., Raposo, C., Zirwes, E.A., Osterwald, A., Pavlovic, A., Moes, S., Beck, J., Nettekoven, M., Benito-Cuesta, I., Grande, T., Drawnel, F., Widmer, G., Holzer, D., van der Wel, T., Mandhair, H., Honer, M., Fingerle, J., Scheffel, J., Broichhagen, J., Gawrisch, K., Romero, J., Hillard, C.J., Varga, Z.V., van der Stelt, M., Pacher, P., Gertsch, J., Ullmer, C., McCormick, P.J., Oddi, S., Spaink, H.P., Maccarrone, M., Veprintsev, D.B., Carreira, E.M., Grether, U., Nazaré, M. (2022) Detection of cannabinoid receptor type 2 in native cells and zebrafish with a highly potent, cell-permeable fluorescent probe. Chemical science. 13:5539-5545.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping