Wednesday, January 13, 2021

Steric-Free Bioorthogonal Labeling of Acetylation Substrates Based on a Fluorine–Thiol Displacement Reaction

Zhigang Lyu, Yue Zhao, Zakey Yusuf Buuh, Nicole Gorman, Aaron R. Goldman, Md Shafiqul Islam, Hsin-Yao Tang, and Rongsheng E. Wang*

J. Am. Chem. Soc. 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.

Chemical Specification of E3 Ubiquitin Ligase Engagement by Cysteine-Reactive Chemistry

Roman C. Sarott, Inchul You, Yen-Der Li, Sean T. Toenjes, Katherine A. Donovan, Pooreum Seo, Martha Ordonez, Woong Sub Byun, Muhammad Murtaz...