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 S VI -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 S VI -Fs can be used as a strategy to expand the insights that offer a valuable guide for the design of S VI -F-containing ligands, thus highlighting the opportunity for S VI -Fs to expand the liganded proteome.