Abstract

The applicability of 2,2-bis(ethoxycarbonyl)-3-(pivaloyloxy)propyl and 2- cyano-2-(2-phenylethylaminocarbonyl)-3-(pivaloyloxy)propyl groups as biodegradable protecting agents for the internucleosidic linkages of phosphorothioate antisense oligonucleotides has been studied. For this purpose, protected phosphoromonothioates of thymidylyl-(3→5)-thymidine [Tp(s)T] containing either a bridged or non-bridged sulfur atom have been prepared, and their chemical stability and enzymatic deprotection have been studied.

Keywords: oligonucleotides, antisense, biodegradable, protecting group, hydrolysis, phosphotriester