Life Science Institute, Zhejiang University, Hangzhou 310058, China.
Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Acta Biochim Biophys Sin (Shanghai). 2020 Jul 10;52(7):776-790. doi: 10.1093/abbs/gmaa053.
Protein ubiquitylation plays important roles in many biological activities. Protein ubiquitylation is a unique process that is mainly controlled by ubiquitin ligases. The ubiquitin-proteasome system (UPS) is the main process to degrade short-lived and unwanted proteins in eukaryotes. Many components in the UPS are attractive drug targets. Recent studies indicated that ubiquitin ligases can be employed as tools in proteolysis-targeting chimeras (PROTACs) for drug discovery. In this review article, we will discuss the recent progress of the application of ubiquitin ligases in the PROTAC drug design. We will also discuss advantages and existing problems of PROTACs. Moreover, we will propose a few principles for selecting ubiquitin ligases in PROTAC applications.
蛋白质泛素化在许多生物活动中发挥着重要作用。蛋白质泛素化是一个独特的过程，主要由泛素连接酶控制。泛素-蛋白酶体系统（UPS）是真核生物中降解短寿命和不需要的蛋白质的主要过程。UPS 的许多成分都是有吸引力的药物靶点。最近的研究表明，泛素连接酶可以作为蛋白酶体靶向嵌合体（PROTAC）药物发现中的工具。在这篇综述文章中，我们将讨论泛素连接酶在 PROTAC 药物设计中的最新应用进展。我们还将讨论 PROTACs 的优点和存在的问题。此外，我们将提出在 PROTAC 应用中选择泛素连接酶的几个原则。
