Profiling sulfur(VI) fluorides as reactive functionalities for chemical biology tools and expansion of the ligandable proteome.

A comprehensive profiling of sulfur(VI) fluoride reactivity is reported in the context of fragment binders and optimized probes. The reactivity profile of an SVI-F panel is demonstrated using live cell chemoproteomics. The studies provide an in-depth understanding of how the hydrolytic stability, protein reactivity, and chemoproteomic utility of SVI-Fs can be used as a strategy to expand the insights that offer a valuable guide for the design of SVI-F-containing ligands, thus highlighting the opportunity for SVI-Fs to expand the liganded proteome.