Steric-Free Bioorthogonal Labeling of Acetylation Substrates Based on a Fluorine-Thiol Displacement Reaction.
Zhigang LyuYue ZhaoZakey Yusuf BuuhNicole GormanAaron R GoldmanMd Shafiqul IslamHsin-Yao TangRongsheng E WangPublished in: Journal of the American Chemical Society (2021)
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.
Keyphrases
- positron emission tomography
- pet imaging
- induced apoptosis
- high resolution
- computed tomography
- cell cycle arrest
- high throughput
- histone deacetylase
- electron transfer
- endoplasmic reticulum stress
- cell death
- signaling pathway
- label free
- pet ct
- loop mediated isothermal amplification
- quantum dots
- single cell
- structural basis