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Editorial
. 2018 Jun 27;9(7):584-586.
doi: 10.1021/acsmedchemlett.8b00276. eCollection 2018 Jul 12.

Emerging Utility of Fluorosulfate Chemical Probes

Lyn H Jones  1
Affiliations
Editorial

Emerging Utility of Fluorosulfate Chemical Probes

Lyn H Jones. ACS Med Chem Lett. .

Abstract

Aryl fluorosulfates are finding widespread utility in chemical biology and medicinal chemistry. The context-dependent engagement of tyrosine, lysine, serine, and histidine amino acid residues in functional protein sites has enabled chemogenomic and chemoproteomic techniques that demonstrate considerable promise for drug discovery and biomedical research.

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Conflict of interest statement

The author declares the following competing financial interest(s): L.H.J. is an employee and shareholder of Jnana Therapeutics.

Figures

Figure 1
Figure 1
(a) Electrostatic potential maps of energy-minimized structures of benzenesulfonyl fluoride and benzene fluorosulfate (MolView). The fluorosulfate electrophile is less reactive. (b) Intact protein MS analysis of the reaction of human serum albumin (HSA, 1 μM) with the sulfur(VI)-fluoride fragment (300 μM) after 24 h. (c) Aryl fluorosulfate publication count by year (Scifinder).
Figure 2
Figure 2
(a) Covalent transthyretin modulators TTR-mFS-Probe (labels the TTR Lys15 residue) and the fluorogenic ligand TTR-pFS-Probe. (b) Cocrystal structure of SF-p1 (blue) with DcpS (gray ribbon) showing reaction with Tyr143 (pink) overlaid with a model of FS-p1 (gold) showing proximity to the noncatalytic Ser272 (neighboring histidine triad and Arg294 are highlighted). (c) Fluorosulfates Biaryl-FS-Probe and FS-Probe1 used for chemoproteomic profiling experiments. (d) Sulfurylation of phenols for the preparation of aryl fluorosulfates.
See this image and copyright information in PMC

References

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