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靶向蛋白降解作为基础生物学和药物靶点发现的有力研究工具。

Targeted protein degradation as a powerful research tool in basic biology and drug target discovery.

机构信息

Department of Cancer Biology, Dana Farber Cancer Institute, Boston, MA, USA.

Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.

出版信息

Nat Struct Mol Biol. 2020 Jul;27(7):605-614. doi: 10.1038/s41594-020-0438-0. Epub 2020 Jun 15.

Abstract

Controlled perturbation of protein activity is essential to study protein function in cells and living organisms. Small molecules that hijack the cellular protein ubiquitination machinery to selectively degrade proteins of interest, so-called degraders, have recently emerged as alternatives to selective chemical inhibitors, both as therapeutic modalities and as powerful research tools. These systems offer unprecedented temporal and spatial control over protein function. Here, we review recent developments in this field, with a particular focus on the use of degraders as research tools to interrogate complex biological problems.

摘要

蛋白质活性的控制干扰对于研究细胞和生物体内的蛋白质功能至关重要。小分子可以劫持细胞内的蛋白质泛素化机制,有选择地降解靶蛋白,这些所谓的降解剂最近已经成为选择性化学抑制剂的替代品,无论是作为治疗方式还是作为强大的研究工具。这些系统提供了对蛋白质功能进行前所未有的时间和空间控制。本文综述了该领域的最新进展,特别关注了降解剂作为研究工具在解决复杂生物学问题方面的应用。

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本文引用的文献

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Exploring Targeted Degradation Strategy for Oncogenic KRAS.探索致癌 KRAS 的靶向降解策略。
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