<i>N</i>-Acyl-<i>N</i>-Alkyl Sulfonamide Probes for Ligand-Directed Covalent Labeling of GPCRs: The Adenosine A_2B Receptor as Case Study.

ABSTRACT: Small molecular tool compounds play an essential role in the study of G protein-coupled receptors (GPCRs). However, tool compounds most often occupy the orthosteric binding site, hampering the study of GPCRs upon ligand binding. To overcome this problem, ligand-directed labeling techniques have been developed that leave a reporter group covalently bound to the GPCR, while allowing subsequent orthosteric ligands to bind. In this work, we applied such a labeling strategy to the adenosine A_2B receptor (A_2BAR). We have synthetically implemented the recently reported N-acyl-N-alkyl sulfonamide (NASA) warhead into a previously developed ligand and show that the binding of the A_2BAR is not restricted by NASA incorporation. Furthermore, we have invest

SUBMITTER: Beerkens BLH 

PROVIDER: S-EPMC11267576 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature