化学
蛋白质水解
计算生物学
蛋白酶体
泛素
小分子
泛素连接酶
蛋白质降解
蛋白质组
生物化学
生物
酶
基因
作者
Qiong Li,Li Zhou,Siyuan Qin,Zhao Huang,Bowen Li,Ruolan Liu,Mei Yang,Edouard C. Nice,Haijing Zhu,Canhua Huang
标识
DOI:10.1016/j.ejmech.2023.115447
摘要
The success of inhibitor-based therapeutics is largely constrained by the acquisition of therapeutic resistance, which is partially driven by the undruggable proteome. The emergence of proteolysis targeting chimera (PROTAC) technology, designed for degrading proteins involved in specific biological processes, might provide a novel framework for solving the above constraint. A heterobifunctional PROTAC molecule could structurally connect an E3 ubiquitin ligase ligand with a protein of interest (POI)-binding ligand by chemical linkers. Such technology would result in the degradation of the targeted protein via the ubiquitin-proteasome system (UPS), opening up a novel way of selectively inhibiting undruggable proteins. Herein, we will highlight the advantages of PROTAC technology and summarize the current understanding of the potential mechanisms involved in biotherapeutics, with a particular focus on its application and development where therapeutic benefits over classical small-molecule inhibitors have been achieved. Finally, we discuss how this technology can contribute to developing biotherapeutic drugs, such as antivirals against infectious diseases, for use in clinical practices.
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