用于活细胞中腺苷 A2A 受体光学控制的光致腺苷衍生物

IF 3.5 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

ACS Chemical Biology Pub Date : 2024-11-11 DOI:10.1021/acschembio.4c00583

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

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引用次数: 0

摘要

光药理学（photopharmacology）是一种强大的技术，可用于以高时空分辨率阐明活细胞和动物的细胞功能。腺苷 A2A 受体（A2AR）是一种 G 蛋白偶联受体，在多种组织中均有表达；其失调与失眠和帕金森病等严重疾病有关。因此，详细阐明 A2AR 的生理功能是非常必要的。在本研究中，我们开发了两种以 A2AR 为靶点的光开关配体：photoAd(blue) 和 photoAd(vio)。通过使用 photoAd(vio)，我们成功地展示了紫光照射在活细胞中对 A2AR 的选择性激活，而且具有很高的时空分辨率。

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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.

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来源期刊

ACS Chemical Biology 生物-生化与分子生物学

CiteScore

7.50

自引率

5.00%

发文量

353

审稿时长

3.3 months

期刊介绍： ACS Chemical Biology provides an international forum for the rapid communication of research that broadly embraces the interface between chemistry and biology. The journal also serves as a forum to facilitate the communication between biologists and chemists that will translate into new research opportunities and discoveries. Results will be published in which molecular reasoning has been used to probe questions through in vitro investigations, cell biological methods, or organismic studies. We welcome mechanistic studies on proteins, nucleic acids, sugars, lipids, and nonbiological polymers. The journal serves a large scientific community, exploring cellular function from both chemical and biological perspectives. It is understood that submitted work is based upon original results and has not been published previously.