热休克蛋白90
化学
蛋白质降解
热休克蛋白
蛋白质水解
连接器
细胞生物学
下调和上调
泛素
融合蛋白
生物化学
生物
重组DNA
酶
操作系统
基因
计算机科学
作者
Zhenzhen Li,Siyue Ma,Ling Zhang,Shuxin Zhang,Zhao Ma,Lüpei Du,Minyong Li
标识
DOI:10.1021/acs.jmedchem.2c01648
摘要
Targeted protein degradation (TPD) strategies open up new avenues for therapeutics and provide powerful tools for biological inquiry. Herein, we present a brand-new approach, termed heat shock protein 90 (HSP90)-mediated targeting chimeras (HEMTACs), to induce intracellular protein degradation by bridging a target protein to HSP90 to drive the downregulation of proteins. We successfully showcase HEMTACs for cyclin-dependent kinase 4 and 6 (CDK4/6) by using a flexible linker to connect the targeting warhead of CDK4/6 with the HSP90 ligand. Overall, our study delivers a series of evidence that HEMTACs can serve as a valuable addition to TPD strategies, most prominently proteolysis-targeting chimera technology.
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