蛋白质的化学全合成*

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化学进展 ›› 2007, Vol. 19 ›› Issue (012) : 1866-1882.

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李娟,郑基深,沈非,方葛敏,郭庆祥,刘磊. 蛋白质的化学全合成^[J]. 化学进展, 2007, 19(012): 1866-1882 Li Juan^1,2 Zheng Jishen¹ Shen Fei¹ Fang Gemin¹ Guo Qingxiang² Liu Lei^1,2. Chemical Synthesis of Proteins[J]. Progress in Chemistry*, 2007, 19(012): 1866-1882

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蛋白质的化学全合成^*

李娟^1,2 郑基深¹ 沈非¹ 方葛敏¹ 郭庆祥²刘磊^1,2**

作者信息 +

Chemical Synthesis of Proteins

Li Juan^1,2 Zheng Jishen¹ Shen Fei¹ Fang Gemin¹ Guo Qingxiang² Liu Lei^1,2**

Author information +

文章历史 +

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。

Abstract

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 cannot 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 protein chemical synthesis 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 reviewed the fundamental aspects of cysteine-based native chemical ligation. We also surveyed the very recent progresses 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, lapidated proteins, and glycoproteins were reviewed.

关键词

肽片段连接 / 半胱氨酸 / 硫酯 / 脂蛋白 / 糖蛋白

Key words

peptide ligation / cysteine / thioester / lipidated protein / glycoprotein

中图分类号： Q51 O621.3+3

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