AI Article Synopsis
- - The study highlights the unclear role of CBR tissue expression and signaling in various diseases, prompting new research efforts.
- - Researchers created a powerful fluorescent CBR agonist probe that combines a validated ligand with a silicon-rhodamine fluorophore for increased cell permeability.
- - This probe uniquely maintains affinity for both mouse and human CBR, facilitating CBR detection in live cells and zebrafish, which could enhance the development of CBR-related drugs.
Article Abstract
Despite its essential role in the (patho)physiology of several diseases, CBR tissue expression profiles and signaling mechanisms are not yet fully understood. We report the development of a highly potent, fluorescent CBR 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 CBR. Extensive cross-validation (FACS, TR-FRET and confocal microscopy) set the stage for CBR detection in endogenously expressing living cells along with zebrafish larvae. Together, these findings will benefit clinical translatability of CBR based drugs.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9116301 | PMC |
| http://dx.doi.org/10.1039/d1sc06659e | DOI Listing |
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