生物正交化学
赖氨酸
计算生物学
蛋白质工程
化学
定向进化
合成生物学
药物发现
生物化学
化学生物学
组合化学
纳米技术
酶
生物
点击化学
氨基酸
基因
材料科学
突变体
作者
Guoqing Jin,Yifan Shi,Shivangi Sharma,Wenshe Ray Liu
标识
DOI:10.1021/acs.accounts.5c00401
摘要
ConspectusGenetically encoded lysine (GEK) chemistry has transformed protein engineering by enabling precise and site-specific modifications, which expand lysine's functional landscape beyond its native post-translational modifications (PTMs). Our work has systematically advanced GEK chemistry by developing engineered pyrrolysyl-tRNA synthetase (PylRS) variants that efficiently incorporate diverse lysine (Lys) derivatives with tailored chemical reactivity. By integrating bioorthogonal handles, acyl and electrophilic warheads, photo-cross-linking groups, and PTM mimics, we have established a set of powerful toolkits for protein labeling, functional studies, and Lys-directed drug design. These advances provide precise control over protein structure and function, facilitating the study of epigenetic modifications, enzyme–substrate interactions, and Lys-guided inhibitor development. As GEK chemistry continues to evolve, its integration with structural/synthetic biology and therapeutic innovation will further expand its impact, unlocking new frontiers in chemical biology and precision therapeutics.
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