Photoresponsive Adenosine Derivatives for the Optical Control of Adenosine A2A Receptors in Living Cells

Harufumi Suzuki; Tomohiro Doura; Yuya Matsuba; Yuma Matsuoka; Tsuyoshi Araya; Hidetsugu Asada; So Iwata; Shigeki Kiyonaka

doi:10.1021/acschembio.4c00583

Photoresponsive Adenosine Derivatives for the Optical Control of Adenosine A_2A Receptors in Living Cells

ACS Chem Biol. 2024 Nov 11. doi: 10.1021/acschembio.4c00583. Online ahead of print.

Authors

Harufumi Suzuki¹, Tomohiro Doura¹, Yuya Matsuba¹, Yuma Matsuoka¹, Tsuyoshi Araya², Hidetsugu Asada², So Iwata^{2

3}, Shigeki Kiyonaka^{1

4}

Affiliations

¹ Department of Biomolecular Engineering, Graduate School of Engineering, Nagoya University, Nagoya 464-8603, Japan.
² Department of Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
³ RIKEN SPring-8 Center, Kobe, Hyogo 679-5148, Japan.
⁴ Research Institute for Quantum and Chemical Innovation, Institutes of Innovation for Future Society, Nagoya University, Nagoya 464-8603, Japan.

PMID: 39527802
DOI: 10.1021/acschembio.4c00583

Abstract

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.