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Abstract
Sequence-specific modulation of gene expression for the treatment of diseases has come to reality. Multiple examples of oligodeoxyribonucleotide phosphorothioates, in which one nonbridging oxygen atom of the internucleotide phosphate group of DNA is replaced by a sulfur atom are currently in advanced clinical trials. Recent advances in phosphoramidite coupling chemistry and solid phase synthesis methodology, together with current state of the art large-scale synthesizers, allow complete assembly of a 20-mer deoxyribonucleotide phosphorothioate at 150 mmole scale in just 8 h. Very high average coupling efficiencies (>98.5%) have been achieved at these scales with only 1.75-fold molar amidite excess.
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