A new strategy for the solid-phase synthesis of 5′-thiolated oligodeoxynucleotides

Abstract

A novel procedure is described for the introduction of a masked thiol function at the 5′-terminus of oligodeoxynucleotides. An acetyl-protected thiol linker phosphoramidite has been prepared which can be coupled efficiently to fully protected oligonucleotides using standard solid-phase techniques. Our strategy is elaborated for oligothymidylates and is further illustrated for oligodeoxynucleotides which are base-protected with the 2-(acetoxymethyl)benzoyl group. Rapid base-deprotection can be accomplished in methanolic potassium carbonate which also effects saponification of the thioacetyl ester. The resultant free thiol is reacted in situ with dithiodipyridine to afford pyridyldisulfide-derivatized oligodeoxynucleotides.