We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Copper assisted sequence-specific chemical protein conjugation at a single backbone amide.
- Authors
Guo, Mengzhun; Zhao, Kai; Guo, Liang; Zhou, Rui; He, Qiuju; Lu, Kuan; Li, Tian; Liu, Dandan; Chen, Jinfeng; Tang, Jing; Fu, Xin; Zhou, Jinyun; Zheng, Bei; Mann, Samuel I.; Zhang, Yongdeng; Huang, Jing; Yang, Bing; Zhou, Ting; Lei, Yingjie; Dang, Bobo
- 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.Direct, site-specific methods of protein functionalization are of interest, but challenging due to difficulty in chemically differentiating a single site within a large protein. Here, the authors develop a Copper Assisted Sequence-specific conjugation Tag (CAST) method to achieve rapid, site-specific protein backbone chemical modification with pinpoint accuracy, and prepare various on-demand modified recombinant proteins using CAST.
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-43753-7