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C-terminal modification and functionalization of proteins via a self-cleavage tag triggered by a small molecule

文献类型：期刊论文

作者Zeng, Yue1,4; Shi, Wei4; Liu, Zhi3,4; Xu, Hao3; Liu, Liya4; Hang, Jiaying4; Wang, Yongqin2; Lu, Mengru2; Zhou, Wei2; Huang, Wei1,2,3,4
刊名NATURE COMMUNICATIONS
出版日期2023-11-07
卷号14期号:1页码:13
DOI10.1038/s41467-023-42977-x
通讯作者Tang, Feng(tangfeng2013@simm.ac.cn)
英文摘要The precise modification or functionalization of the protein C-terminus is essential but full of challenges. Herein, a chemical approach to modify the C-terminus is developed by fusing a cysteine protease domain on the C-terminus of the protein of interest, which could achieve the non-enzymatic C-terminal functionalization by InsP6-triggered cysteine protease domain self-cleavage. This method demonstrates a highly efficient way to achieve protein C-terminal functionalization and is compatible with a wide range of amine-containing molecules and proteins. Additionally, a reversible C-terminal de-functionalization is found by incubating the C-terminal modified proteins with cysteine protease domain and InsP6, providing a tool for protein functionalization and de-functionalization. Last, various applications of protein C-terminal functionalization are provided in this work, as demonstrated by the site-specific assembly of nanobody drug conjugates, the construction of a bifunctional antibody, the C-terminal fluorescent labeling, and the C-terminal transpeptidation and glycosylation. Specific modification or functionalization of proteins at the C-terminus is of interest but remains challenging. Here, the authors report an approach for the efficient modification of C-terminus by fusion of the cysteine protease domain (CPD) on the C-terminus of the protein of interest, and subsequent functionalization with amine-containing molecules triggered by InsP6-mediated CPD self-cleavage.
WOS关键词BUTELASE 1 ; PEPTIDE ; BIOCONJUGATION ; ACTIVATION ; HYDRAZIDES ; VERSATILE ; LIGATION ; TYROSINE
资助项目This work was supported by the National Key Research and Development Plan grant (2021YEE0200500), the Natural Science Foundation of China (NSFC, No. 92153301, 82003574, 82204183, 22277126, and 82325045), the Shanghai Sail Program (No. 22YF1457400), the Spe[2021YEE0200500] ; National Key Research and Development Plan grant[92153301] ; National Key Research and Development Plan grant[82003574] ; National Key Research and Development Plan grant[82204183] ; National Key Research and Development Plan grant[22277126] ; National Key Research and Development Plan grant[82325045] ; Natural Science Foundation of China (NSFC)[22YF1457400] ; Shanghai Sail Program ; Special Research Assistant Program (Chinese Academy of Sciences, CAS)[TD2020005] ; Hangzhou innovation and entrepreneurship leading team project[2021M700158] ; China Postdoctoral Science Foundation[LG-QS-202206-03] ; Lingang Laboratory ; SANOFI Scholarship Program
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:001103881600012
出版者NATURE PORTFOLIO
源URL[http://119.78.100.183/handle/2S10ELR8/308526]  
专题新药研究国家重点实验室
通讯作者Tang, Feng
作者单位1.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China
2.Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China
3.Nanjing Univ Chinese Med, Sch Chinese Mat Med, 138 Xianlin Rd, Nanjing 210023, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Biotherapeut Discovery Res, State Key Lab Drug Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Zeng, Yue,Shi, Wei,Liu, Zhi,et al. C-terminal modification and functionalization of proteins via a self-cleavage tag triggered by a small molecule[J]. NATURE COMMUNICATIONS,2023,14(1):13.
APA Zeng, Yue.,Shi, Wei.,Liu, Zhi.,Xu, Hao.,Liu, Liya.,...&Tang, Feng.(2023).C-terminal modification and functionalization of proteins via a self-cleavage tag triggered by a small molecule.NATURE COMMUNICATIONS,14(1),13.
MLA Zeng, Yue,et al."C-terminal modification and functionalization of proteins via a self-cleavage tag triggered by a small molecule".NATURE COMMUNICATIONS 14.1(2023):13.

入库方式： OAI收割

来源：上海药物研究所

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