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.

Automated summary

A comprehensive profiling of sulfur(VI) fluoride reactivity is presented, focusing on fragment binders and optimized probes. The reactivity profile of S-VI-Fs is demonstrated through live cell chemoproteomics. The studies provide insights into the hydrolytic stability, protein reactivity, and chemoproteomic utility of S-VI-Fs, offering a valuable guide for designing ligands containing S-VI-Fs and expanding the liganded proteome.