基因编码非天然氨基酸技术及其在生物医学领域的应用  

Genetic incorporation of unnatural amino acids into proteins and its translational application in biomedicine

作　　者：朱银雪 王德祥 孔影 陆文捷 叶慧[1] 郝海平[1] ZHU Yinxue;WANG Dexiang;KONG Ying;LU Wenjie;YE Hui;HAO Haiping(Key Laboratory of Drug Metabolism and Pharmacokinetics,China Pharmaceutical University,Nanjing 210009,China)

机构地区：[1]中国药科大学药物代谢动力学重点实验室,南京210009

出　　处：《中国药科大学学报》2022年第4期383-391,共9页Journal of China Pharmaceutical University

基　　金：国家自然科学基金资助项目(No.82173783,No.81930109,No.81720108032);中央高校基本科研业务费资助项目(No.2632022YC03)。

摘　　要：人体内蛋白质通常由20种天然氨基酸组成。氨基酸的不同排列组合及立体构象是构建丰富多样性的蛋白质的基础。近年来开发的突破性基因密码子拓展技术通过向目标蛋白质中定向引入非天然氨基酸,能够赋予原有的靶蛋白以共价结合邻近蛋白质、携带荧光基团、模拟蛋白质的翻译后修饰等新的生物学特性。本文从非天然氨基酸的结构和功能出发,介绍了不同类型的非天然氨基酸分别在调节蛋白质稳定性、研究蛋白质构象、表达水平、定位以及识别和增强蛋白质间亲和作用等方面的用途。此外,基因编码非天然氨基酸技术在生物医学领域的应用前景,将为生物药物的设计及优化提供全新的思路和方法。Proteins in the human body are usually made of 20 natural amino acids. Through different amino acid combinations and isomerization, proteins of diverse functions are built. An emerging genetic code expansion technology can introduce unnatural amino acids into specific sites of target protein, endowing the protein with new biological characteristics including covalently binding with proximal proteins, carrying fluorescence, and mimicking specific protein post-translational modifications. In this paper, based on the structure and function of unnatural amino acids, the applications of different types of unnatural amino acids in regulating protein’s stability,studying protein’s conformation, expression level, and localization, and uncovering heretofore unknown proteinprotein interactions were reviewed. Besides, genetic code expansion of unnatural amino acids is anticipated to find broad utilities in biomedicine by bringing new ideas and methods to the design and optimization of biologics.

关 键 词：非天然氨基酸 基因密码子拓展技术 蛋白质 反应性 荧光基团 翻译后修饰 生物药物 

分 类 号：Q78[生物学—分子生物学]