Photoresponsive Adenosine Derivatives for the Optical Control of Adenosine A2AReceptors in Living Cells

The use of photoresponsive ligands to optically control proteins of interest, known as photopharmacology, is a powerful technique for elucidating cellular function in living cells and animals with a high spatiotemporal resolution. The adenosine A2Areceptor (A2AR) is a G protein-coupled receptor that is expressed in various tissues; its dysregulation is implicated in severe diseases such as insomnia and Parkinson’s disease. A detailed elucidation of the physiological function of A2AR is, therefore, highly desirable. In the present study, we developed two photoswitchable ligands, photoAd(blue) and photoAd(vio), that target A2AR. Using photoAd(vio), we successfully demonstrated the selective activation of A2AR in living cells by violet-light irradiation with high spatiotemporal resolution.