Divergent synthesis and identification of the cellular targets of deoxyelephantopins

作者：Lagoutte Roman; Serba Christelle; Abegg Daniel; Hoch Dominic G; Adibekian Alexander^*; Winssinger Nicolas^*

来源：Nature Communications, 2016, 7(1): 12470.

DOI：10.1038/ncomms12470

Herbal extracts containing sesquiterpene lactones have been extensively used in traditional medicine and are known to be rich in a, b-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 PPARg activity in situ via covalent engagement of a cysteine residue in the zinc-finger motif of this nuclear receptor.

• 出版日期2016-8