Bibliographic Details
| Title: |
Development of subtype-selective covalent ligands for the adenosine A2Breceptor by tuning the reactive groupElectronic supplementary information (ESI) available. See DOI: https://doi.org/10.1039/d2md00132b |
| Authors: |
Beerkens, Bert L. H., Wang, Xuesong, Avgeropoulou, Maria, Adistia, Lisa N., van Veldhoven, Jacobus P. D., Jespers, Willem, Liu, Rongfang, Heitman, Laura H., IJzerman, Adriaan P., van der Es, Daan |
| Source: |
MedChemComm; 2022, Vol. 13 Issue: 7 p850-856, 7p |
| Abstract: |
Signalling through the adenosine receptors (ARs), in particular through the adenosine A2Breceptor (A2BAR), has been shown to play a role in a variety of pathological conditions, ranging from immune disorders to cancer. Covalent ligands for the A2BAR have the potential to irreversibly block the receptor, as well as inhibit all A2BAR-induced signalling pathways. This will allow a thorough investigation of the pathophysiological role of the receptor. In this study, we synthesized and evaluated a set of potential covalent ligands for the A2BAR. The ligands all contain a core scaffold consisting of a substituted xanthine, varying in type and orientation of electrophilic group (warhead). Here, we find that the right combination of these variables is necessary for a high affinity, irreversible mode of binding and selectivity towards the A2BAR. Altogether, this is the case for sulfonyl fluoride 24(LUF7982), a covalent ligand that allows for novel ways to interrogate the A2BAR. |
| Database: |
Supplemental Index |
