Activation-Free Sulfonyl Fluoride Probes for Fragment Screening

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...

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Published in:Molecules (Basel, Switzerland) Switzerland), 2023-03, Vol.28 (7), p.3042
Main Authors: Petri, László, Ábrányi-Balogh, Péter, Csorba, Noémi, Keeley, Aaron, Simon, József, Ranđelović, Ivan, Tóvári, József, Schlosser, Gitta, Szabó, Dániel, Drahos, László, Keserű, György M
Format: Article
Language:English
Subjects:
Amino acids
Amino Acids - chemistry
Biology
chemical probe
Chemical properties
Chemistry
covalent fragment
electrophilic warhead
Fluorides
Fluorides - chemistry
fragment screening
Fragments
Labeling
Libraries
Mass Spectrometry
Mass spectroscopy
Methods
Pharmaceutical chemistry
Proteins
Reagents
Residues
Sulfinic Acids - chemistry
sulfonyl fluoride
targeted covalent inhibitor
Warheads
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cited_by cdi_FETCH-LOGICAL-c561t-771ebd061262e32414aa062f704cda7518687a6f289551858ec9a0d945c0be493
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creator Petri, László
Ábrányi-Balogh, Péter
Csorba, Noémi
Keeley, Aaron
Simon, József
Ranđelović, Ivan
Tóvári, József
Schlosser, Gitta
Szabó, Dániel
Drahos, László
Keserű, György M
description 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.
doi_str_mv 10.3390/molecules28073042
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subjects Amino acids
Amino Acids - chemistry
Biology
chemical probe
Chemical properties
Chemistry
covalent fragment
electrophilic warhead
Fluorides
Fluorides - chemistry
fragment screening
Fragments
Labeling
Libraries
Mass Spectrometry
Mass spectroscopy
Methods
Pharmaceutical chemistry
Proteins
Reagents
Residues
Sulfinic Acids - chemistry
sulfonyl fluoride
targeted covalent inhibitor
Warheads
title Activation-Free Sulfonyl Fluoride Probes for Fragment Screening
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