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Profiling Sulfur(VI) Fluorides as Reactive Functionalities for Chemical Biology Tools and Expansion of the Ligandable Proteome.

ABSTRACT: 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.

SUBMITTER: Gilbert KE

PROVIDER: S-EPMC9942091 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Profiling Sulfur(VI) Fluorides as Reactive Functionalities for Chemical Biology Tools and Expansion of the Ligandable Proteome.

Gilbert Katharine E KE Vuorinen Aini A Aatkar Arron A Pogány Peter P Pettinger Jonathan J Grant Emma K EK Kirkpatrick Joanna M JM Rittinger Katrin K House David D Burley Glenn A GA Bush Jacob T JT

ACS chemical biology 20230117 2

Here, 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 inv ...[more]

PMID: 36649130

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