Divergent synthesis and identification of the cellular targets of deoxyelephantopins.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 27539788.
- Also identified by DOI 10.1038/ncomms12470 and PMC identifier 4992173.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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.
Medical subject headings
- Antineoplastic Agents
- Apoptosis
- Cell Proliferation
- Lactones
- PPAR gamma
- Sesquiterpenes