A NEW STRATEGY FOR THE SOLID-PHASE SYNTHESIS OF 5'-THIOLATED OLIGODEOXYNUCLEOTIDES

A novel procedure is described for the introduction of a masked thiol function at the 5'-terminus of oligodeoxynucleotides. An acetyl-protec ted thiol linker phosphoramidite has been prepared which can be couple d efficiently to fully protected oligonucleotides using standard solid -phase techniques. Our strategy is elaborated for oligothymidylates an d is further illustrated for oligodeoxynucleotides which are base-prot ected with the 2-(acetoxymethyl)benzoyl group. Rapid base-deprotection can be accomplished in methanolic potassium carbonate which also effe cts saponification of the thioacetyl ester. The resultant free thiol i s reacted in situ with dithiodipyridine to afford pyridyldisulfide-der ivatized oligodeoxynucleotides.