Résumé
Dithymidine phosphate, phosphorothiolate, phosphorothionate and phosphorodithioate triesters (1 to 4) bearing the tert-butyl S-acyl-thiolethyl (tBu-SATE) bioreversible protecting group were synthesized, Their stability in culture medium (CM) and in total CEM cell extract (TCE) was evaluated, We showed that these dimers have a high stability in CM and are selectively hydrolyzed in TCE by carboxyesterase activities to the corresponding parent dimer, The stability of the chimeric prooligonucleotide 10 was also evaluated in both CM and TCE. This species contains a central gap of three phosphorodithioate linkages, alkylated with the bioreversible Me-SATE protecting group, and two neutral methylphosphonate flanks. In each case, the hydrolysis selectively yielded the parent oligo with a good stability in culture medium (t(1/2) = 32 h). In cell extract, the hydrolysis of the first bioreversible group takes place with a half-life of 15 min and the fully deprotected oligo was obtained with a half-life of 80 min.