Photoresponsive Adenosine Derivatives for the Optical Control of Adenosine A_2A Receptors 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 A_2A receptor (A_2AR) 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 A_2AR is, therefore, highly desirable. In the present study, we developed two photoswitchable ligands, photoAd­(blue) and photoAd­(vio), that target A_2AR. Using photoAd­(vio), we successfully demonstrated the selective activation of A_2AR in living cells by violet-light irradiation with high spatiotemporal resolution.