Profiling Sulfur(VI) Fluorides as Reactive Functionalities for Chemical Biology Tools and Expansion of the Ligandable Proteome
Katharine Gilbert, Aini Vuorinen, Arron Aatkar, Péter Pogány, Jonathan Pettinger, Emma K. Grant, Joanna Kirkpatrick, Katrin Rittinger, David House, Glenn A. Burley, Jacob T. Bush
Abstract
High Resolution Image Download MS PowerPoint Slide Here, we report a comprehensive profiling of sulfur(VI) fluorides (S VI -Fs) as reactive groups for chemical biology applications. S VI -Fs are reactive functionalities that modify lysine, tyrosine, histidine, and serine sidechains. A panel of S VI -Fs were studied with respect to hydrolytic stability and reactivity with nucleophilic amino acid sidechains. The use of S VI -Fs to covalently modify carbonic anhydrase II (CAII) and a range of kinases was then investigated. Finally, the S VI -F panel was used in live cell chemoproteomic workflows, identifying novel protein targets based on the type of S VI -F used. This work highlights how S VI -F reactivity can be used as a tool to expand the liganded proteome.