Deoxy-adenosine-monophosphate (dAMP) di-n-butylester induces apoptosis by increasing the dATP level in HL-60 cells

Deoxy-ATP is a potent inducer of apoptosis. We intended to synthesize a lipophilic dAMP derivative which, according to our working hypothesis penetrates into the cell, is converted to dAMP by intracellular esterases and to dATP by nucleotide kinases. We synthesized dAMP-di-n-butylester (DAB) and tested it. We found that it fulfills the above-described expectations. DAB treatment decreases the viability of HL-60 cells, increases the dATP concentration and induces apoptogenic cytochrome c release from mitochondria with concomitant elevation of caspase-9 activity. Our results indicate that use of dAMP derivatives with masked phosphate may be a feasible approach for pharmacological elevation of intracellular dATP and induction of apoptosis.