Because polyamines are critically involved in the proliferation of neoplastic tissues, enzymes in their synthetic pathway present rational targets for the development of anticancer agents. AdoDATO is a potent and specific transition-state analog inhibitor of the key polyamine biosynthetic enzyme, spermidine synthase, and in in vitro systems leads to the inhibition of cell proliferation via polyamine depletion. In order to evaluate the in vivo effectiveness of AdoDATO, the synthesis of this inhibitor has been scaled up using the reported procedure. This paper describes the development of a preparative HPLC procedure for the purification of AdoDATO by paired-ion chromatography. This methodology could also be used to purify other strongly basic compounds that contain hydrophobic regions.
PDF full text from Publisher