Insufficiently charged isosteric analogue of spermine: interaction with polyamine uptake, and effect on Caco-2 cell growth.

We characterised a novel, charge-insufficient isosteric analogue of spermine, 11-[(amino)oxy]-4,9-diaza-1-aminoundecane (AOSPM). This analogue was synthesised by displacing aminopropyl group by aminooxyethyl group, the latter having pK(a) of about 5. Charge deficiency of the AOSPM molecule was fixed at a definite atom, while pK(a) of the rest nitrogen was similar to the parent polyamine. AOSPM competed with putrescine, spermidine and spermine for the uptake into the cell, and was accumulated in the cells in high amounts when exogenous polyamine synthesis was impaired. It was not recognised by the cells as growth-promoting polyamine, since it was unable to restore growth arrest due to polyamine deprivation. Like natural spermine, this polyamine analogue prevented oxidative DNA damage. AOSPM could be used not only as a tool to study polyamine homeostasis in the cell, but may have distinct applications either as radiation protector, a stable and non-toxic inhibitor of polyamine uptake or, as an appropriate vector, to enhance the uptake of impermeable compounds into the cell.