Synthesis of Biotinylated Episilvestrol: Highly Selective Targeting of the Translation Factors eIF4AI/II
Synthesis of Biotinylated Episilvestrol: Highly Selective Targeting of the Translation Factors eIF4AI/II
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DOI：
10.1021/ol400401d
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发表时间：
2013-03-15
期刊：
影响因子：
5.2
通讯作者：
Rizzacasa, Mark A.
中科院分区：
文献类型：
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作者：
Chambers, Jennifer M.;Lindqvist, Lisa M.;Rizzacasa, Mark A.
Silvestrol（1）和episilvestrol（2）是蛋白质合成抑制剂，前者已在多种小鼠癌症模型中显示出疗效;然而，尚未描述这些强效细胞毒性天然产物的选择性。在此，证明了真核起始因子eIF 4AI/II是通过亲和纯化检测到的唯一结合司维司群（1）和生物素化表司维司群（9）的蛋白质。我们的研究证明了这些有前途的化疗药物的显着选择性。
Silvestrol (1) and episilvestrol (2) are protein synthesis inhibitors, and the former has shown efficacy in multiple mouse models of cancer; however, the selectivity of these potent cytotoxic natural products has not been described. Herein, it is demonstrated that eukaryotic initiation factors eIF4AI/II were the only proteins detected to bind silvestrol (1) and biotinylated episilvestrol (9) by affinity purification. Our study demonstrates the remarkable selectivity of these promising chemotherapeutics.