Activation-Free Sulfonyl Fluoride Probes for Fragment Screening.

Content Provider	Europe PMC
Author	Petri, László Ábrányi-Balogh, Péter Csorba, Noémi Keeley, Aaron Simon, József Ranđelović, Ivan Tóvári, József Schlosser, Gitta Szabó, Dániel Drahos, László Keserű, György M.
Editor	Liu, Dan
Copyright Year	2023
Abstract	SuFEx chemistry is based on the unique reactivity of the sulfonyl fluoride group with a range of nucleophiles. Accordingly, sulfonyl fluorides label multiple nucleophilic amino acid residues, making these reagents popular in both chemical biology and medicinal chemistry applications. The reactivity of sulfonyl fluorides nominates this warhead chemotype as a candidate for an external, activation-free general labelling tag. Here, we report the synthesis and characterization of a small sulfonyl fluoride library that yielded the 3-carboxybenzenesulfonyl fluoride warhead for tagging tractable targets at nucleophilic residues. Based on these results, we propose that coupling diverse fragments to this warhead would result in a library of sulfonyl fluoride bits (SuFBits), available for screening against protein targets. SuFBits will label the target if it binds to the core fragment, which facilitates the identification of weak fragments by mass spectrometry.
Journal	Molecules
Volume Number	28
DOI	10.3390/molecules28073042
PubMed Central reference number	PMC10096327
Issue Number	7
PubMed reference number	37049805
e-ISSN	14203049
Language	English
Publisher	Molecular Diversity Preservation International (MDPI)
Publisher Date	2023-03-29
Access Restriction	Open
Subject Keyword	chemical probe covalent fragment electrophilic warhead fragment screening sulfonyl fluoride targeted covalent inhibitor
Content Type	Text
Resource Type	Article
Subject	Physical and Theoretical Chemistry Medicine Chemistry Drug Discovery Pharmaceutical Science Analytical Chemistry Molecular Medicine Organic Chemistry