基于遗传密码扩增技术的生物医药开发及应用  

Development and Application of Biomedicine based on Genetic Code Expansion Technology

作　　者：苏桃根 邹卓锦 宋潇达[1] 刘玮[1] SU Taogen;ZOU Zhuojin;SONG Xiaoda;LIU Wei(School of Life Science and Technology,China Pharmaceutical University,Nanjing 210009,China)

机构地区：[1]中国药科大学生命科学与技术学院,江苏南京211198

出　　处：《药物生物技术》2024年第3期306-312,共7页Pharmaceutical Biotechnology

基　　金：国家自然基金青年基金(No.21907107);江苏高校优势学科建设工程资助项目支持。

摘　　要：遗传密码扩增是将具有不同活性基团的非天然氨基酸引入到蛋白质的特定位点的化学生物学技术。非天然氨基酸具有的不同基团,可以赋予蛋白质独特的生物活性。遗传密码扩增技术的关键是与宿主内源氨酰tRNA合成酶-tRNA对正交的酶对(aaRS/tRNA),通过对aaRS/tRNA进行定向进化,可以实现在靶蛋白序列中定点引入非天然氨基酸。文章从古菌吡咯赖氨酸氨酰tRNA合成酶对(PylRS/tRNAPyl CUA)出发,介绍了能够引入的不同类型非天然氨基酸和对应的突变位点,以及在生物正交反应、翻译后修饰、生物偶联及生物治疗领域的部分应用。遗传密码扩增技术在生物医药领域具有广泛的应用范围及前景,这将为生物药物的设计开发提供全新的策略。The technique of genetic code expansion in chemical biology involves the incorporation of non-natural amino acids,modified with various functional groups,at specific sites within proteins.These non-natural amino acids possess diverse functional groups that confer unique biological activities upon the proteins.Central to genetic code expansion technology is an orthogonal enzyme pair for the host's endogenous aminoacyl tRNA synthetase-tRNA pair(aaRS/tRNA).Through directed evolution of aaRS/tRNA,this technology enables site-specific introduction of non-natural amino acids into target protein sequences.Starting from PylRS/tRNAPyl CUA,the utilization of different types of non-natural amino acids and their corresponding mutation sites,as well as applications in biological orthogonality,post-translational modification,biological coupling,and biotherapy were discussed.Genetic code expansion technology holds great promise for a wide range of applications in biomedicine and offers a new strategy for designing and developing biological drugs.

关 键 词：遗传密码扩增 非天然氨基酸 生物正交 翻译后修饰 生物偶联 生物治疗 

分 类 号：Q51[生物学—生物化学]