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

03 February 2022, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

Chemical probes are valuable tools to explore the function of proteins. Incorporation of electrophiles into small molecules enables covalent capture of protein interactions and provides access to powerful technologies including chemoproteomic profiling and reactive fragment screening. Current approaches have been largely limited to protein pockets containing cysteine, so establishing strategies to target other amino acid residues is essential to expanding the applicability across the proteome. Here, we profiled sulfur(VI) fluorides (SVI-F) as reactive functionalities that can modify multiple residues including Lys, Tyr, His and Ser, thus offering utility for targeting almost any protein. These studies provided an in-depth understanding of SVI-F functionalities, including hydrolytic stability, protein reactivity and utility in chemoproteomics. Such insights offer a valuable guide for the prospective design of SVI-F-containing ligands for various chemical biology workflows and illustrate the wide range of proteins that SVI-Fs can capture, thus highlighting the opportunity for SVI-Fs to expand the liganded proteome.

Keywords

covalent probes
sulfonyl fluoride
chemical biology
covalent fragment screening

Supplementary materials

Title
Description
Actions
Title
Supplementary information
Description
Supplementary figures; experimental methods including synthesis and characterisation of new compounds; computational methods.
Actions

Comments

Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.