Optical Control of Small Molecule-Induced Protein Degradation
Optical Control of Small Molecule-Induced Protein Degradation
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DOI：
10.1021/jacs.9b12718
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发表时间：
2020-02-05
影响因子：
15
通讯作者：
Deiters, Alexander
中科院分区：
文献类型：
--
作者：
Naro, Yuta;Darrah, Kristie;Deiters, Alexander
作为一种新兴的蛋白质扰动方法，小分子诱导的蛋白质降解作为一种化学工具和潜在的治疗手段受到了极大的关注。为了实现对其功能的离散控制，我们开发了一种广泛适用的方法，用于小分子诱导的蛋白质降解的光学激活。通过在两种不同的配体上安装两种不同的光致保护基团，即所谓的笼化基团，以招募Von hipel - lindau （VHL）和小脑（CRBN） E3泛素连接酶，我们的策略使任何小分子弹头的光触发蛋白质降解成为可能。
As an emerging approach to protein perturbation, small molecule-induced protein degradation has gained significant attention as both a chemical tool and a potential therapeutic. To enable discrete control over its function, we have developed a broadly applicable approach for the optical activation of small molecule-induced protein degradation. By installing two different photolabile protecting groups, so-called caging groups, onto two different ligands recruiting Von Hippel-Lindau (VHL) and cereblon (CRBN) E3 ubiquitin ligases, our strategy enables light-triggered protein degradation for any small molecule warhead.