AI Article Synopsis
- The leukotriene B4 receptor 2 (BLT2) is a potential target for improving diabetic wound healing and treating gastrointestinal issues, activated by a specific compound called 12-HHT.
- This study focused on creating a fluorescent probe from the synthetic BLT2 agonist CAY10583, facilitating various fluorescence-based research techniques.
- The research demonstrated that the developed fluorescent ligands can effectively bind to the BLT2 receptor and influence its signaling, making them valuable tools for studying BLT2 pharmacology.
Article Abstract
The leukotriene B4 receptor 2 (BLT2) is a G-protein coupled receptor activated by 12()-hydroxyheptadeca-5,8,10-trienoic acid (12-HHT), which has been proposed as a promising therapeutic target for diabetic wound healing and gastrointestinal lesions. In this study, the rational design of a fluorescent probe based on the synthetic BLT2 agonist CAY10583 is described. The synthesis of several derivatives of CAY10583 coupled to fluorescein resulted in a traceable ligand suitable for different fluorescence-based techniques. An HTRF-based displacement assay (Tag-lite) on stably transfected CHO-K1 cells was developed to characterize binding properties of diverse BLT2 ligands. Highly specific binding to the BLT2 receptor was demonstrated in staining experiments on mouse skin tissue, and specific modulation of BLT2-induced cAMP signaling provided further evidence for receptor binding and ligand functionality. In conclusion, the fluorescent ligands developed in this study are suitable to investigate the pharmacology of BLT2 receptor ligands in a variety of assay systems.
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| http://dx.doi.org/10.1021/acs.jmedchem.1c01589 | DOI Listing |
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