生物正交化学
四嗪
化学
标签
生物化学
组合化学
点击化学
有机化学
作者
Daniel Richter,Edgars Laķis,Jörn Piel
出处
期刊:Nature Chemistry
[Springer Nature]
日期:2023-07-03
卷期号:15 (10): 1422-1430
被引量:9
标识
DOI:10.1038/s41557-023-01252-8
摘要
Abstract The tetrazine ligation is an inverse electron-demand Diels–Alder reaction widely used for bioorthogonal modifications due to its versatility, site specificity and fast reaction kinetics. A major limitation has been the incorporation of dienophiles in biomolecules and organisms, which relies on externally added reagents. Available methods require the incorporation of tetrazine-reactive groups by enzyme-mediated ligations or unnatural amino acid incorporation. Here we report a tetrazine ligation strategy, termed TyrEx (tyramine excision) cycloaddition, permitting autonomous dienophile generation in bacteria. It utilizes a unique aminopyruvate unit introduced by post-translational protein splicing at a short tag. Tetrazine conjugation occurs rapidly with a rate constant of 0.625 (15) M −1 s −1 and was applied to produce a radiolabel chelator-modified Her2-binding Affibody and intracellular, fluorescently labelled cell division protein FtsZ. We anticipate the labelling strategy to be useful for intracellular studies of proteins, as a stable conjugation method for protein therapeutics, as well as other applications.
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