Investigation of the mechanism of action of a potent pateamine A analog, des-methyl, des-amino pateamine A (DMDAPatA).

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.