Copper assisted sequence-specific chemical protein conjugation at a single backbone amide

Autor: Mengzhun Guo, Kai Zhao, Liang Guo, Rui Zhou, Qiuju He, Kuan Lu, Tian Li, Dandan Liu, Jinfeng Chen, Jing Tang, Xin Fu, Jinyun Zhou, Bei Zheng, Samuel I. Mann, Yongdeng Zhang, Jing Huang, Bing Yang, Ting Zhou, Yingjie Lei, Bobo Dang
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Nature Communications, Vol 14, Iss 1, Pp 1-10 (2023)
Druh dokumentu: article
ISSN: 2041-1723
61723304
DOI: 10.1038/s41467-023-43753-7
Popis: Abstract Direct, site-specific methods of protein functionalization are highly desirable for biotechnology. However, such methods are challenging due to the difficulty of chemically differentiating a single site within a large protein. Herein, we propose “metal binding targeting” strategy and develop a Copper Assisted Sequence-specific conjugation Tag (CAST) method to achieve rapid (second order rate 8.1 M−1 s−1), site-specific protein backbone chemical modification with pinpoint accuracy. We demonstrate the versatility of CAST conjugation by preparing various on-demand modified recombinant proteins, including a homogeneous antibody-drug conjugate with high plasma stability and potent efficacy in vitro and in vivo. Thus, CAST provides an efficient and quantitative method to site-specifically attach payloads on large, native proteins.
Databáze: Directory of Open Access Journals
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