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bioRxiv · 10.1101/2020.09.09.290221

Steric-Free Bioorthogonal Labeling of Acetylation Substrates Based on a Fluorine-Thiol Displacement Reaction (FTDR)

Lyu, Z.·Zhao, Y.·Buuh, Z. Y.·Gorman, N.·Goldman, A. R.·Islam, M. S.·Tang, H.-Y.·Wang, R. E.
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Abstract

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 al- kyne- 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 (PTMs) in a systematic manner.

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Lyu, Z., Zhao, Y., Buuh, Z. Y., Gorman, N., Goldman, A. R., Islam, M. S., Tang, H.-Y., Wang, R. E.. 2020-09-09. Steric-Free Bioorthogonal Labeling of Acetylation Substrates Based on a Fluorine-Thiol Displacement Reaction (FTDR). https://doi.org/10.1101/2020.09.09.290221

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