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Abstract
Here, we report a comprehensive profiling study of sulfur(VI) fluorides (SVI-F) in the context of multiple chemical biology applications and illustrate that these motifs present an exciting opportunity to develop tools for a wide scope of protein targets. SVI-Fs are reactive functionalities that offer utility for targeting almost any protein, as they can modify multiple residues including Lys, Tyr, His and Ser. A panel of SVI-F functionalities were studied with respect to hydrolytic stability and reactivity with nucleophilic amino acids. Subsequently, the reactivity of SVI-Fs with CAII and kinase proteins was investigated, in the context of both fragment binders and optimized probes. Finally, the performance of the SVI-F panel in chemoproteomic workflows was analyzed. The studies provided an in-depth understanding of the hydrolytic stability, protein reactivity and chemoproteomic utility of SVI-F functionalities that are suitable for direct incorporation into chemical tools. Such insights offer a valuable guide for the prospective design of SVI-F-containing ligands for various chemical biology workflows and demonstrate the wide range of proteins that SVI-Fs can capture, thus highlighting the opportunity for SVI-Fs to expand the liganded proteome.
Original language | English |
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Pages (from-to) | 285-295 |
Number of pages | 11 |
Journal | ACS Chemical Biology |
Volume | 18 |
Issue number | 2 |
Early online date | 17 Jan 2023 |
DOIs | |
Publication status | Published - 17 Feb 2023 |
Keywords
- profiling
- sulfur (VI) fluorides
- reactive functionalities
- chemical biology tools
- ligandable proteome
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Dive into the research topics of 'Profiling sulfur(VI) fluorides as reactive functionalities for chemical biology tools and expansion of the ligandable proteome'. Together they form a unique fingerprint.Projects
- 1 Finished
Activities
- 1 Invited talk
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LINXS Chemistry of Life Meeting
Glenn Burley (Speaker)
18 Oct 2024Activity: Talk or presentation types › Invited talk