Katharine E. Gilbert, Aini Vuorinen, Arron Aatkar, Peter Pogány, Jonathan Pettinger, Emma K. Grant, Joanna M. Kirkpatrick, Katrin Rittinger, David House, Glenn A. Burley, and Jacob T. Bush
ACS Chemical Biology 2023
DOI: 10.1021/acschembio.2c00633Here, we report a comprehensive profiling of sulfur(VI) fluorides (SVI-Fs) as reactive groups for chemical biology applications. SVI-Fs are reactive functionalities that modify lysine, tyrosine, histidine, and serine sidechains. A panel of SVI-Fs were studied with respect to hydrolytic stability and reactivity with nucleophilic amino acid sidechains. The use of SVI-Fs to covalently modify carbonic anhydrase II (CAII) and a range of kinases was then investigated. Finally, the SVI-F panel was used in live cell chemoproteomic workflows, identifying novel protein targets based on the type of SVI-F used. This work highlights how SVI-F reactivity can be used as a tool to expand the liganded proteome.
