SpringerProtocols: Abstract: Dimethylthiarum Disulfide: New Sulfur Transfer Reagent in Phosphorothioates Oligonucleotide Synthesis

Dimethylthiarum Disulfide: New Sulfur Transfer Reagent in Phosphorothioates Oligonucleotide Synthesis

By: Zhiwei Wang², Quanlai Song², Yogesh S. Sanghvi³

Abstract

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Dimethylthiarum disulfide (DTD) has been developed as a new and efficient sulfur-transfer reagent for automated synthesis of phosphorothioate oligonucleotides using phosphoramidite chemistry. The traditional four-step automated oligonucleotide synthesis has been compressed to three-step protocol using DTD. This improvement allowed an overall 20% reduction in the solvent consumption and reduced the total synthesis time by 25%. The large-scale application of DTD has been successfully demonstrated by synthesis of therapeutically useful 20-mer phosphorothioate antisense oligonucleotides with excellent yield and purity.

Affiliation(s): (2) Medicinal Chemistry Department, ISIS Pharmaceuticals, Carlsbad, CA
(3) Rasayan Inc., Encinitas, CA

Book Title: Oligonucleotide Synthesis

Series: Methods in Molecular Biology | Volume: 288 | Pub. Date: Sep-01-2004 | Page Range: 51-63 | DOI: 10.1385/1-59259-823-4:051

Subject: Biochemistry

Key Words: Dimethylthiarum disulfide (DTD) - phenylacetyl disulfide (PADS) - sulfur-transfer reagent - phosphorothioate oligonucleotides - phosphoramidite chemistry - antisense - solid-phase synthesis

References

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