蛋白质的化学全合成  

Chemical Synthesis of Proteins

作　　者：李娟[1] 郑基深[1] 沈非[1] 方葛敏[1] 郭庆祥[2] 刘磊[1] 

机构地区：[1]清华大学化学系生命有机磷与化学生物学教育部重点实验室,北京100084 [2]中国科学技术大学化学系,合肥230026

出　　处：《化学进展》2007年第12期1866-1882,共17页Progress in Chemistry

基　　金：国家自然科学基金项目(No.20472079)资助

摘　　要：含有非天然氨基酸的蛋白质(如翻译后修饰蛋白质、修饰有探针分子的蛋白质等)是化学生物学中重要的生理活性分子。这些分子难以通过生物表达来获取,而必须使用化学方法来合成。半胱氨酸肽片段连接方法是目前应用于蛋白质化学全合成中的一种重要方法,该方法能够在温和的水溶液中高效地实现肽片段的连接,从而生成天然或者非天然的蛋白质。本文系统地综述了半胱氨酸肽片段连接方法的基本原理,详细讨论了近年来人们对该方法的一些重要改进。最后又介绍了该方法在几类重要的蛋白质分子合成中的代表性应用。Proteins that contain non-natural amino acid residues （such as post-translationally modified proteins and proteins functionalized with synthetic probes） are highly important molecules in chemical biology. These molecules can＇t be readily obtained through biological expression, so that the only approach to produce them is to use chemical synthesis. Currently the most important method in the field of chemical synthesis of protein is cysteine-based native chemical ligation, which can efficiently condense peptide segments in aqueous solutions under mild conditions to generate natural as well as non-natural proteins. Here we systematically review the fundamental aspects of cysteine-based native chemical ligation. We also surveyed the recent progress in this field to improve the efficiency and scope of this particular ligation method. Finally, the representative applications of the ligation method in the synthesis of natural proteins, lipidated proteins, and glycoproteins are introduced.

关 键 词：肽片段连接 半胱氨酸 硫酯 脂蛋白 糖蛋白 

分 类 号：Q51[生物学—生物化学] O621.33[理学—有机化学]