期刊
RSC CHEMICAL BIOLOGY
卷 2, 期 2, 页码 450-467出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/d0cb00215a
关键词
-
资金
- US National Institutes of Health [GM129468]
Ubiquitination is a crucial protein post-translational modification process in eukaryotes. The enzymatic approach for ubiquitination has limitations, sparking interest in developing chemical methods for generating ubiquitinated proteins. These new chemical methods provide crucial tools for understanding the Ub system and developing novel therapeutics.
Ubiquitination is an important protein post-translational modification regulating many cellular processes in eukaryotes. Ubiquitination is catalyzed by a three-enzyme cascade resulting in the conjugation of the C-terminal carboxylate of ubiquitin (Ub) to the epsilon-amino group of a lysine residue in the acceptor protein via an isopeptide bond. In vitro enzymatic ubiquitination utilizing Ub ligases has been successfully employed to generate Ub dimers and polymers. However, limitations of the enzymatic approach exist, particularly due to the requirement of specific Ub ligase for any given target protein and the low catalytic efficiency of the Ub ligase. To achieve an in-depth understanding of the molecular mechanism of Ub signaling, new methods are needed to generate mono- and poly-ubiquitinated proteins at a specific site with defined polyubiquitin chain linkage and length. Chemical methods offer an attractive solution to the above-described challenges. In this review, we summarize the recently developed chemical methods for generating ubiquitinated proteins using synthetic and semisynthetic approaches. These new tools and approaches, as an important part of the Ub toolbox, are crucial to our understanding and exploitation of the Ub system for novel therapeutics.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据