泛素化蛋白的化学合成及半合成

The chemical and semi-synthesis of ubquitinated protein

蛋白质翻译后修饰(post-translational modifications,PTMs)在调节蛋白质的结构和功能上发挥着重要作用,异常的蛋白质翻译后修饰会导致某些疾病的发生.泛素化(ubiquitination)作为一类重要的蛋白质翻译后修饰,已经被证明与细胞的稳态以及细胞内部的多条信号通路有关,主要参与细胞内蛋白的定位、调节和降解以及细胞周期、基因表达、信号传递、损伤修复、炎症免疫等多种生命过程.然而,对于泛素蛋白的相关研究虽然进行了多年,但是许多重要的科学问题尚未研究清楚,其中如何高效地获得大量、均一的泛素化蛋白是最重要的挑战之一.近年来,蛋白质化学合成及半合成手段的发展,很大程度上解决了这一难题.本文主要针对目前常用的泛素化蛋白的化学合成和半合成方法进行综述.

Protein posttranslational modifications （PTMs） play an essential role in regulating protein’s structure and function, while abnormal PTMs can cause diseases. Ubiquitination is one of the most important PTMs in eukaryotes, and is involeved in a wide range of cellular processes, such as the protein location in the cell, regulation and degradation as well as the cell cycle, gene expression, cellular signal transduction, damage repair, inflammation, immune and other life processes. However, despite of several decades of studies, several important questions remain unsolved. A major hurdle is the difficulty to obtain homogeneous ubiquitinated proteins in sufficient amounts. Recently, the chemical and semi-synthetic strategies offer solutions to overcome the obstacle. In this review, we survey the widely used methods for the chemical and semi-synthesis of ubiquitinated proteins.