Divergent synthesis and identification of the cellular targets of deoxyelephantopins.
Divergent synthesis and identification of the cellular targets of deoxyelephantopins.
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DOI：
10.1038/ncomms12470
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发表时间：
2016-08-19
影响因子：
16.6
通讯作者：
Winssinger N
中科院分区：
文献类型：
--
作者：
Lagoutte R;Serba C;Abegg D;Hoch DG;Adibekian A;Winssinger N
含有倍半萜内酯的草药提取物在传统医学中被广泛使用，并且富含α，β-不饱和功能，可以共价结合靶蛋白。在这里，我们报告的合成方法，以获得脱氧象皮苷的类似物，具有抗癌特性的倍半萜内酯。利用炔标记细胞探针和定量蛋白质组学分析，我们确定了脱氧象皮素的几个细胞靶点。我们进一步证明脱氧象皮素通过与核受体锌指基序中的半胱氨酸残基共价结合来原位拮抗PPARγ活性。脱氧象皮素是一种天然存在的倍半萜内酯，具有已知的抗癌特性。在这里，作者合成脱氧象皮素和一系列类似物，包括炔标记探针，使用它们来识别其细胞目标。
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. Deoxyelephantopin is a naturally occurring sesquiterpene lactone with known anticancer properties. Here, the authors synthesize deoxyelephantopins and a range of analogues including alkyne-tagged probes, using them to identify its cellular targets.