Divergent synthesis and identification of the cellular targets of deoxyelephantopins

Herbal extracts containing sesquiterpene lactones have been extensively used in traditional medicine and are known to be rich in α,β-unsaturated functionalities that can covalently engage target proteins. Here we report synthetic methodologies to access analogues of deoxyelephantopin, a sesquiterpen...

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Autores principales: Lagoutte, Roman, Serba, Christelle, Abegg, Daniel, Hoch, Dominic G., Adibekian, Alexander, Winssinger, Nicolas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4992173/
https://www.ncbi.nlm.nih.gov/pubmed/27539788
http://dx.doi.org/10.1038/ncomms12470
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author Lagoutte, Roman
Serba, Christelle
Abegg, Daniel
Hoch, Dominic G.
Adibekian, Alexander
Winssinger, Nicolas
author_facet Lagoutte, Roman
Serba, Christelle
Abegg, Daniel
Hoch, Dominic G.
Adibekian, Alexander
Winssinger, Nicolas
author_sort Lagoutte, Roman
collection PubMed
description Herbal extracts containing sesquiterpene lactones have been extensively used in traditional medicine and are known to be rich in α,β-unsaturated functionalities that can covalently engage target proteins. Here we report synthetic methodologies to access analogues of deoxyelephantopin, a sesquiterpene lactone with anticancer properties. Using alkyne-tagged cellular probes and quantitative proteomics analysis, we identified several cellular targets of deoxyelephantopin. We further demonstrate that deoxyelephantopin antagonizes PPARγ activity in situ via covalent engagement of a cysteine residue in the zinc-finger motif of this nuclear receptor.
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spelling pubmed-49921732016-09-01 Divergent synthesis and identification of the cellular targets of deoxyelephantopins Lagoutte, Roman Serba, Christelle Abegg, Daniel Hoch, Dominic G. Adibekian, Alexander Winssinger, Nicolas Nat Commun Article Herbal extracts containing sesquiterpene lactones have been extensively used in traditional medicine and are known to be rich in α,β-unsaturated functionalities that can covalently engage target proteins. Here we report synthetic methodologies to access analogues of deoxyelephantopin, a sesquiterpene lactone with anticancer properties. Using alkyne-tagged cellular probes and quantitative proteomics analysis, we identified several cellular targets of deoxyelephantopin. We further demonstrate that deoxyelephantopin antagonizes PPARγ activity in situ via covalent engagement of a cysteine residue in the zinc-finger motif of this nuclear receptor. Nature Publishing Group 2016-08-19 /pmc/articles/PMC4992173/ /pubmed/27539788 http://dx.doi.org/10.1038/ncomms12470 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Lagoutte, Roman
Serba, Christelle
Abegg, Daniel
Hoch, Dominic G.
Adibekian, Alexander
Winssinger, Nicolas
Divergent synthesis and identification of the cellular targets of deoxyelephantopins
title Divergent synthesis and identification of the cellular targets of deoxyelephantopins
title_full Divergent synthesis and identification of the cellular targets of deoxyelephantopins
title_fullStr Divergent synthesis and identification of the cellular targets of deoxyelephantopins
title_full_unstemmed Divergent synthesis and identification of the cellular targets of deoxyelephantopins
title_short Divergent synthesis and identification of the cellular targets of deoxyelephantopins
title_sort divergent synthesis and identification of the cellular targets of deoxyelephantopins
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4992173/
https://www.ncbi.nlm.nih.gov/pubmed/27539788
http://dx.doi.org/10.1038/ncomms12470
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