Advances in the optimization of the linker in proteolysis-targeting chimeras (PROTAC)
10.16438/j.0513-4870.2020-1272
- VernacularTitle:蛋白水解靶向嵌合体 (PROTAC) 连接链优化的研究进展
- Author:
Xin-yuan SHENG
;
Shi-hui WU
;
Bao-lin LI
;
Xu-nuo LI
;
Hao-shu WU
;
Ji CAO
- Publication Type:Research Article
- Keywords:
proteolysis targeting chimeras;
linker;
E3 enzyme-proteolysis targeting chimeras-protein of interest ternary complex;
egradation efficacy;
substrate selectivity
- From:
Acta Pharmaceutica Sinica
2021;56(2):445-455
- CountryChina
- Language:Chinese
-
Abstract:
With high selectivity and potency, target protein degradation technology has recently emerged as a strategy for drug discovery and design. Proteolysis-targeting chimeras (PROTAC) function as inducers for the degradation of target proteins and are a research focus in drug development. Current research on PROTAC mainly revolves around the rational design of PROTAC molecules, the discovery of new E3 ubiquitin ligase ligands and improvement in drug targeting. In this review, we focus on the PROTAC linker and its effects on the generation of the E3 enzyme-PROTAC-target protein ternary complex from three standpoints: length, binding site and chemical properties. We discuss the influences of the linker on the efficacy and the selectivity of PROTAC molecules.
