Promiscuous inhibitors of tyrosine protein kinases, proteases and phosphatases are useful reagents for probing regulatory pathways and stabilizing lysates as well as starting points for the design of more selective agents. Ubiquitination regulates many critical cellular processes, and promiscuous inhibitors of deubiquitinases (DUBs) would be similarly valuable. The currently available promiscuous DUB inhibitors are highly reactive electrophilic compounds that can crosslink proteins. Herein we introduce diarylcarbonate esters as a novel class of promiscuous DUB inhibitors that do not have the liabilities associated with the previously reported compounds. Diarylcarbonates stabilize the high molecular weight ubiquitin pools in cells and lysates. They also elicit cellular phenotypes associated with DUB inhibition, demonstrating their utility in ubiquitin discovery. Diarylcarbonates may also be a useful scaffold for the development of specific DUB inhibitors.

中文翻译：

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碳酸二芳基酯是一类新的去泛素化酶抑制剂。

酪氨酸蛋白激酶，蛋白酶和磷酸酶的混杂抑制剂是用于探索调节途径和稳定裂解物的有用试剂，也是设计更多选择性试剂的起点。泛素化调节许多关键的细胞过程，而去泛素酶（DUBs）的混杂抑制剂也同样有价值。当前可用的混杂DUB抑制剂是可以使蛋白质交联的高反应性亲电子化合物。本文中，我们引入碳酸二芳基酯作为一类新的混杂DUB抑制剂，它不具有与先前报道的化合物相关的责任。碳酸二芳基酯稳定细胞和裂解物中的高分子量泛素库。他们还引发了与DUB抑制相关的细胞表型，证明了它们在泛素发现中的效用。碳酸二芳基酯也可能是开发特定DUB抑制剂的有用支架。