The natural product pateamineA (PatA) is a highly potent antiproliferative agent. PatA and the simplified analog desmethyl, desamino pateamineA (DMDAPatA) have exhibited cytotoxicity selective for rapidly proliferating cells, and have been shown to inhibit cap-dependent translation initiation through binding to eIF4A (eukaryotic initiation factor 4A) of the eIF4F complex. PatA and DMDAPatA are both known to stimulate the RNA-dependent ATPase, and ATP-dependent RNA helicase activities of eIF4A. The impact of other eIF4F components, eIF4E and eIF4G, on DMDAPatA action were investigated in vitro and in cultured mammalian cells. The perturbation of the eIF4A-eIF4G association was found to be eIF4E- and mRNA cap-dependent. An inhibitory effect on helicase activity of eIF4A was observed when it was part of a complex that mimicked the eIF4F complex. We propose a model of action for DMDAPatA (and by supposition PatA) where the cellular activity of the compound is dependent on an "active" eIF4F complex.

中文翻译：

---

研究有效的三聚氰胺A类似物，去甲基，三聚氨基乙酰胺A（DMDAPatA）的作用机理。

天然产品帕他明A（PatA）是一种高效的抗增殖剂。PatA和简化的类似物desmethyl，desamino pateamineA（DMDAPatA）对快速增殖的细胞表现出选择性的细胞毒性，并已显示出通过与eIF4F复合体的eIF4A（真核起始因子4A）结合而抑制帽依赖性翻译起始。已知PatA和DMDAPatA均可刺激eIF4A的RNA依赖性ATPase和ATP依赖性RNA解旋酶活性。在体外和培养的哺乳动物细胞中研究了其他eIF4F成分eIF4E和eIF4G对DMDAPatA作用的影响。发现eIF4A-eIF4G关联的扰动是eIF4E和mRNA帽依赖性的。当它是模仿eIF4F复合物的复合物的一部分时，观察到对eIF4A的解旋酶活性有抑制作用。