Biolabile constructs for pronucleotide design

After summarising the in vitro and in vivo results obtained with nucleotide prodrugs (pronucleotides) bearing two S-acyl-2-thioethyl (SATE) groups as esterase-labile phosphate protections, we will describe recent work on mononucleoside mixed phosphoester derivatives. These new series of biolabile constructs were designed to lead to the selective intracellular delivery of the corresponding 5′-mononucleotide through different enzyme-mediated activation steps.

Three series of biolabile constructs (mixed SATE pronucleotides) were designed for the delivery of the corresponding 5′-mononucleotide inside cells. Synthesis of these mononucleoside derivatives (phosphotriesters, phosphoramidates and phosphorothiolates) involves both PIII and PV chemistries.Figure optionsDownload as PowerPoint slide