PMID- 36649130 OWN - NLM STAT- MEDLINE DCOM- 20230222 LR - 20230226 IS - 1554-8937 (Electronic) IS - 1554-8929 (Print) IS - 1554-8929 (Linking) VI - 18 IP - 2 DP - 2023 Feb 17 TI - Profiling Sulfur(VI) Fluorides as Reactive Functionalities for Chemical Biology Tools and Expansion of the Ligandable Proteome. PG - 285-295 LID - 10.1021/acschembio.2c00633 [doi] AB - 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. FAU - Gilbert, Katharine E AU - Gilbert KE AD - GlaxoSmithKline, Gunnels Wood Road, Stevenage, HertfordshireSG1 2NY, United Kingdom. AD - University of Strathclyde, 295 Cathedral Street, GlasgowG11XL, United Kingdom. FAU - Vuorinen, Aini AU - Vuorinen A AD - Crick-GSK Biomedical LinkLabs, GlaxoSmithKline, Gunnels Wood Road, StevenageSG1 2NY, United Kingdom. FAU - Aatkar, Arron AU - Aatkar A AD - GlaxoSmithKline, Gunnels Wood Road, Stevenage, HertfordshireSG1 2NY, United Kingdom. AD - University of Strathclyde, 295 Cathedral Street, GlasgowG11XL, United Kingdom. FAU - Pogany, Peter AU - Pogany P AD - GlaxoSmithKline, Gunnels Wood Road, Stevenage, HertfordshireSG1 2NY, United Kingdom. FAU - Pettinger, Jonathan AU - Pettinger J AD - Crick-GSK Biomedical LinkLabs, GlaxoSmithKline, Gunnels Wood Road, StevenageSG1 2NY, United Kingdom. FAU - Grant, Emma K AU - Grant EK AD - GlaxoSmithKline, Gunnels Wood Road, Stevenage, HertfordshireSG1 2NY, United Kingdom. FAU - Kirkpatrick, Joanna M AU - Kirkpatrick JM AUID- ORCID: 0000-0001-9291-7294 AD - The Francis Crick Institute, 1 Midland Road, LondonNW1 1AT, United Kingdom. FAU - Rittinger, Katrin AU - Rittinger K AUID- ORCID: 0000-0002-7698-4435 AD - The Francis Crick Institute, 1 Midland Road, LondonNW1 1AT, United Kingdom. FAU - House, David AU - House D AUID- ORCID: 0000-0002-9635-2451 AD - GlaxoSmithKline, Gunnels Wood Road, Stevenage, HertfordshireSG1 2NY, United Kingdom. AD - Crick-GSK Biomedical LinkLabs, GlaxoSmithKline, Gunnels Wood Road, StevenageSG1 2NY, United Kingdom. FAU - Burley, Glenn A AU - Burley GA AUID- ORCID: 0000-0002-4896-113X AD - University of Strathclyde, 295 Cathedral Street, GlasgowG11XL, United Kingdom. FAU - Bush, Jacob T AU - Bush JT AUID- ORCID: 0000-0001-7165-0092 AD - GlaxoSmithKline, Gunnels Wood Road, Stevenage, HertfordshireSG1 2NY, United Kingdom. AD - Crick-GSK Biomedical LinkLabs, GlaxoSmithKline, Gunnels Wood Road, StevenageSG1 2NY, United Kingdom. LA - eng GR - Medical Research Council/United Kingdom GR - Cancer Research UK/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230117 PL - United States TA - ACS Chem Biol JT - ACS chemical biology JID - 101282906 RN - 0 (Proteome) RN - Q80VPU408O (Fluorides) RN - 70FD1KFU70 (Sulfur) RN - 0 (Amino Acids) SB - IM MH - *Proteome/metabolism MH - *Fluorides/chemistry MH - Sulfur/chemistry MH - Amino Acids/chemistry MH - Biology PMC - PMC9942091 COIS- The authors declare no competing financial interest. EDAT- 2023/01/18 06:00 MHDA- 2023/02/22 06:00 PMCR- 2023/02/21 CRDT- 2023/01/17 12:23 PHST- 2023/01/18 06:00 [pubmed] PHST- 2023/02/22 06:00 [medline] PHST- 2023/01/17 12:23 [entrez] PHST- 2023/02/21 00:00 [pmc-release] AID - 10.1021/acschembio.2c00633 [doi] PST - ppublish SO - ACS Chem Biol. 2023 Feb 17;18(2):285-295. doi: 10.1021/acschembio.2c00633. Epub 2023 Jan 17.