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化学进展 2012, Vol. 24 Issue (04): 577-588 前一篇   后一篇

• 综述与评论 •

蛋白质功能化新策略:嵌入非天然氨基酸

张春秋, 罗全, 刘俊秋, 沈家骢   

  1. 吉林大学超分子结构与材料国家重点实验室 长春 130012
  • 收稿日期:2011-08-01 修回日期:2011-12-01 出版日期:2012-04-24 发布日期:2012-02-08
  • 基金资助:

    国家自然科学基金项目(No.91027023,20874036,20921003,21004028)、国家杰出青年基金项目(No.20725415);国家重点基础研究发展计划(973)项目(No.2007CB808006)资助

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New Strategies for Protein Functionalization: Inserting Unnatural Amino Acids into Proteins

Zhang Chunqiu, Luo Quan, Liu Junqiu, Shen Jiacong   

  1. State Key Laboratory of Supramolecular Structure and Materials, Jilin University, Changchun 130012, China
  • Received:2011-08-01 Revised:2011-12-01 Online:2012-04-24 Published:2012-02-08
天然蛋白质由20种天然氨基酸组成,这些蛋白质的构筑基元包含功能基团:羧基、氨基、巯基、硫醚、羟基、碱性胺、烷基和芳基。然而,这些有限的功能基团却不足以完成生物体内所有的生物学功能。为了更好地让生命的体现者--蛋白质完成更加精确和多样的生物学功能,自然界会对蛋白质进行翻译后的修饰,包括:磷酸化,甲基化,乙酰化或者羟基化,甚至在某些情况下,进化出一种新型的翻译机制以便插入硒代半胱氨酸或者吡咯霉素。受此启发,生物化学家发展出各种生物或化学方法来改变或插入新的蛋白质构筑基元,使天然蛋白质完成其相应的生物学功能或者使其具有某些特殊的性质,甚至是创造一种新酶。该文将简单介绍这些蛋白质修饰策略以及该领域的最新进展。
关键词： 天然氨基酸, 非天然氨基酸, 蛋白质
Although 20 natural amino acids served as the building blocks of proteins contain several functional groups including carboxylic acids, amides, thiols, thiol ethers, alcohols, basic amines, and alkyl and aryl groups, they are still unable to carry out all of the natural functions. In order to improve the precision and diversity of protein to perform the biological processes, organisms have provided a variety of posttranslational modifications including phosphorylation, methylation, acetylation, and hydroxylation, even evolved novel translational machinery to incorporate either selenocysteine or pyrrolysine. Inspired by biological system, many biological or chemical methods have been developed to alter or insert new building blocks into protein, which enable protein to perform relevant functions or have some special properties, even create a new kind of enzyme. Here, we give a brief overview of the strategies for protein modification and the latest progress in this field.
Contents
1 Introduction
2 Chemical approaches
2.1 Chemical modification of proteins
2.2 Chemical synthesis
2.3 Semisynthesis
3 Biosynthetic approaches in vitro
4 Biosynthetic approaches in vivo
4.1 Incorporating unnatural amino acids into proteins using auxotrophic bacterial strains
4.2 Expanding genetic code
5 Functionalization and applications
5.1 'Click’ chemistry
5.2 Alkyne and azide functionalization
5.3 Keto and aldehyde functionalization
5.4 Alkene functionalization
5.5 Other functional unnatural amino acids
6 Conclusion and prospects
Key words: natural amino acids, unnatural amino acids, proteins

中图分类号: 

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