Blue Light Activated Rapamycin for Optical Control of Protein Dimerization in Cells and Zebrafish Embryos,ACS Chemical Biology

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Blue Light Activated Rapamycin for Optical Control of Protein Dimerization in Cells and Zebrafish Embryos
ACS Chemical Biology ( IF 3.5 ) Pub Date : 2021-10-05 , DOI: 10.1021/acschembio.1c00547
Taylor M Courtney ₁ , Kristie E Darrah ₁ , Trevor J Horst ₁ , Michael Tsang ₂ , Alexander Deiters ₁

Affiliation

Rapamycin-induced dimerization of FKBP and FRB is the most commonly utilized chemically induced protein dimerization system. It has been extensively used to conditionally control protein localization, split-enzyme activity, and protein–protein interactions in general by simply fusing FKBP and FRB to proteins of interest. We have developed a new aminonitrobiphenylethyl caging group and applied it to the generation of a caged rapamycin analog that can be photoactivated using blue light. Importantly, the caged rapamycin analog shows minimal background activity with regard to protein dimerization and can be directly interfaced with a wide range of established (and often commercially available) FKBP/FRB systems. We have successfully demonstrated its applicability to the optical control of enzymatic function, protein stability, and protein subcellular localization. Further, we also showcased its applicability toward optical regulation of cell signaling, specifically mTOR signaling, in cells and aquatic embryos.

中文翻译：

蓝光激活雷帕霉素对细胞和斑马鱼胚胎中蛋白质二聚化的光学控制

雷帕霉素诱导的 FKBP 和 FRB 二聚化是最常用的化学诱导蛋白质二聚化系统。它已被广泛用于通过简单地将 FKBP 和 FRB 与感兴趣的蛋白质融合来有条件地控制蛋白质定位、分裂酶活性和蛋白质-蛋白质相互作用。我们开发了一种新的氨基硝基联苯乙基笼状基团，并将其应用于可使用蓝光光激活的笼状雷帕霉素类似物的生成。重要的是，笼式雷帕霉素类似物在蛋白质二聚化方面显示出最小的背景活性，并且可以直接与广泛的已建立（并且通常是市售的）FKBP/FRB 系统连接。我们已经成功地证明了它在酶功能的光学控制、蛋白质稳定性、和蛋白质亚细胞定位。此外，我们还展示了其在细胞和水生胚胎中对细胞信号，特别是 mTOR 信号的光学调节的适用性。

更新日期：2021-11-19

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