Palladium-Mediated Cleavage of Proteins with Thiazolidine-Modified Backbone in Live Cells
Palladium-Mediated Cleavage of Proteins with Thiazolidine-Modified Backbone in Live Cells
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DOI：
10.1002/anie.201906545
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发表时间：
2019-08-23
影响因子：
16.6
通讯作者：
Brik, Ashraf
中科院分区：
文献类型：
--
作者：
Mann, Guy;Satish, Gandhesiri;Brik, Ashraf
化学蛋白质合成和双正交修饰化学允许生产用于一系列生物学研究的独特蛋白质。用于位点选择性蛋白质标记的键形成反应通常用于这些努力中。然而，选择性键断裂反应的探索要少得多，仍然是一个巨大的挑战。此外，大多数研究都是通过全合成或半合成制备修饰蛋白，主要用于体外实验，对活细胞的扩展非常有限。这里报道的是一种研究独特的修饰蛋白质的方法，该蛋白质含有无痕细胞递送单元和用于化学活化的钯基可切割元件，并监测这些蛋白质在活细胞中的作用。这种方法被证明用于合成笼状泛素-醛，其被脱笼用于抑制活细胞中的去泛素化酶。
Chemical protein synthesis and biorthogonal modification chemistries allow production of unique proteins for a range of biological studies. Bond-forming reactions for site-selective protein labeling are commonly used in these endeavors. Selective bond-cleavage reactions, however, are much less explored and still pose a great challenge. In addition, most of studies with modified proteins prepared by either total synthesis or semisynthesis have been applied mainly for in vitro experiments with very limited extension to live cells. Reported here is an approach for studying uniquely modified proteins containing a traceless cell delivery unit and palladium-based cleavable element for chemical activation, and monitoring the effect of these proteins in live cells. This approach is demonstrated for the synthesis of a caged ubiquitin-aldehyde, which was decaged for the inhibition of deubiquitinases in live cells.