Department of Chemistry, Temple University, 1901 N. 13th Street, Philadelphia, Pennsylvania 19122, United States.
Proteomics and Metabolomics Facility, The Wistar Institute, Philadelphia, Pennsylvania 19104, United States.
J Am Chem Soc. 2021 Jan 27;143(3):1341-1347. doi: 10.1021/jacs.0c05605. Epub 2021 Jan 12.
We have developed a novel bioorthogonal reaction that can selectively displace fluorine substitutions alpha to amide bonds. This fluorine-thiol displacement reaction (FTDR) allows for fluorinated cofactors or precursors to be utilized as chemical reporters, hijacking acetyltransferase-mediated acetylation both in vitro and in live cells, which cannot be achieved with azide- or alkyne-based chemical reporters. The fluoroacetamide labels can be further converted to biotin or fluorophore tags using FTDR, enabling the general detection and imaging of acetyl substrates. This strategy may lead to a steric-free labeling platform for substrate proteins, expanding our chemical toolbox for functional annotation of post-translational modifications in a systematic manner.
我们开发了一种新颖的生物正交反应，可以选择性地取代酰胺键α位的氟取代基。这种氟-硫取代反应（FTDR）可以将氟化辅助因子或前体用作化学报告物，劫持乙酰转移酶介导的体外和活细胞中的乙酰化，这是无法用叠氮化物或炔烃基化学报告物实现的。氟乙酰胺标记物可以进一步通过 FTDR 转化为生物素或荧光团标记物，从而能够普遍检测和成像乙酰化底物。该策略可能会为底物蛋白提供一个无空间位阻的标记平台，以系统的方式扩展我们用于翻译后修饰功能注释的化学工具包。
