The prooligonucleotide approach. I: Esterase-mediated reversibility of dithymidine S-alkyl-phosphorothiolates to dithymidine phosphorothioates

Alkylation of dithymidine phosphorothioate and phosphorodithioate with various iodoalkyl acylates afforded the corresponding uncharged S-alkyl phosphoromono- and di-thioates respectively. Upon incubation of these triesters in CEM cell extracts, the bioreversible alkyl acylate masking groups were selectively and rapidly removed by carboxyesterases present in the milieu, yielding the starting dinucleoside diesters