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

• Published in: Tetrahedron Vol. 49; no. 47; pp. 10931 - 10944
• Main Authors: Kuijpers, Will H.A., van Boeckel, Constant A.A.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 1993; Elsevier
• Subjects: Carbohydrates. Nucleosides and nucleotides; Chemistry; Chemistry, Organic; Exact sciences and technology; Nucleosides, nucleotides and oligonucleotides; Organic chemistry; Physical Sciences; Preparations and properties; Science & Technology; ATTACHMENT; OLIGODEOXYRIBONUCLEOTIDES; AMINO; THIOL SPECIFIC PROBES; OLIGONUCLEOTIDES; Purine nucleotide; Organic disulfide; Nitrogen heterocycle; Six membered ring; Dinucleotide; Oligonucleotide; Solid phase; Deoxyribonucleotide; Oligodeoxyribonucleotide; Pyrimidine nucleotide; Pyridine derivatives
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/S0040-4020(01)80247-7

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. The preparation of a thioacetyl linker phosphoramidite is described which enables the introduction of a pyridyldisulfide function at the 5′-terminus of oligodeoxynucleotides.