Imperial College London

Professor Matthew J. Fuchter

Faculty of Natural SciencesDepartment of Chemistry

Professor of Chemistry
 
 
 
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Contact

 

+44 (0)20 7594 5815m.fuchter

 
 
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Location

 

401CMolecular Sciences Research HubWhite City Campus

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Summary

 

Publications

Citation

BibTex format

@article{Chavas:2018:10.1021/acschembio.8b00530,
author = {Chavas, TEJ and Fuchter, MJ and DiMaggio, PA},
doi = {10.1021/acschembio.8b00530},
journal = {ACS Chemical Biology},
pages = {2897--2907},
title = {Unbiased mass spectrometry elucidation of the targets and mechanisms of activity-based probes: A case study involving sulfonyl fluorides},
url = {http://dx.doi.org/10.1021/acschembio.8b00530},
volume = {13},
year = {2018}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - The elucidation of protein/drug interactions remains a major challenge in drug discovery. Liquid chromatography–tandem mass spectrometry has emerged as a tremendously powerful technology for this endeavor, but its full potential has yet to be realized owing in part to unresolved challenges in data analysis. Herein, we demonstrate how tandem mass spectrometry can comprehensively map small molecule/peptide adducts when combined with unconstrained sequencing. Using a published sulfonyl fluoride activity-based probe as a model system, this method enabled the discovery of several unreported sites of interaction with its target proteins. Crucially, this probe was found to undergo quantitative displacement and hydrolysis from the target protein’s active site. Isotopic labeling experiments provided a mechanistic rationale for the observed hydrolysis that involves neighboring-group participation. A chemical biology tagging strategy that leverages the probe’s observed lability was developed and shown to be compatible with the original small molecule inhibitor in discovery profiling experiments.
AU - Chavas,TEJ
AU - Fuchter,MJ
AU - DiMaggio,PA
DO - 10.1021/acschembio.8b00530
EP - 2907
PY - 2018///
SN - 1554-8929
SP - 2897
TI - Unbiased mass spectrometry elucidation of the targets and mechanisms of activity-based probes: A case study involving sulfonyl fluorides
T2 - ACS Chemical Biology
UR - http://dx.doi.org/10.1021/acschembio.8b00530
UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000448488600010&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR - http://hdl.handle.net/10044/1/64894
VL - 13
ER -