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Nucleic Acids Research, 2000, Vol. 28, No. 9 E40-e40
© 2000 Oxford University Press

Highly efficient solid phase synthesis of oligonucleotide analogs containing phosphorodithioate linkages

Daniel C. Capaldi, Douglas L. Cole and Vasulinga T. Ravikumar*

Isis Pharmaceuticals, 2292 Faraday Avenue, Carlsbad, CA 92008, USA

A triester method for the synthesis of deoxynucleoside phosphorodithioate dimers is described. The phosphorodithioate linkage is introduced using a new dithiophosphorylating reagent DPSE-SP(S)Cl2 where DPSE = 2-diphenylmethylsilylethyl. This group is removed quickly using tetra-butylammonium fluoride leading to the quantitative formation of phosphoro­dithioate diesters uncontaminated with the corresponding phosphorothioates. The utility of this group is demonstrated by the synthesis of a penta­decathymidylic acid, [T(PS2)T(PO2)]7T, which contains alternating phosphorodithioate/phosphate diester internucleotide linkages.

* To whom correspondence should be addressed. Tel: +1 760 603 2412; Fax: +1 760 929 0528; Email: vravikumar@isisph.com


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