摘要
近年来,合成蛋白水解靶向嵌合体(proteolysis targeting chimeric molecule,PROTAC)作为一种新颖的诱导蛋白降解策略引起了药物化学家们的广泛关注。这种双能嵌合分子通过连接体将靶蛋白配体与E3连接酶配体连接,招募E3至靶蛋白表面,引发多聚泛素化过程诱导蛋白降解。这种策略已经成功降解多种与人类疾病相关的蛋白质,并具有高效能、高选择性、以及靶向"不可成药"蛋白等优势。本文将重点介绍PROTACs技术的独特优势和研究进展,以及设计PROTAC分子时亟待解决的难题。
Recently,a new class of molecules has attracted the attention of pharmaceutical chemists,which is called proteolysis targeting chimeric molecules (PROTACs). These heterobifunctional molecules are designed to connect target protein ligand to E3 ligase ligand via a linker. By hijacking the E3 ligase,PROTACs facilitate substrate poly-ubiquitination and induce protein degradation. This strategy has been applied to a variety of proteins successfully and there are advantages of high efficacy,selectivity and ability to target 'undruggable 'proteins. We reviewed PROTAC technology from the unique advantages,recent progress and problems to be solved when we design PROTAC molecules.
作者
梁倩倩
曹亚权
杨鹏
李亚楠
LIANG Qian-qian;CAO Ya-quan;YANG Peng;LI Ya-nan(School of Pharmacy,Zhengzhou University,Zhengzhou 450001,China)
出处
《中国新药杂志》
CAS
CSCD
北大核心
2019年第4期442-450,共9页
Chinese Journal of New Drugs
关键词
蛋白水解靶向嵌合体
泛素化
降解剂
靶点
药物设计
proteolysis targeting chimeric molecule(PROTAC)
ubiquitination
degarder
target
drug design
