Synthesis of phosphorodithioate DNA by the H-phosphonothioate method

A novel method for the efficient synthesis phosphorodithioate DNA using H-phosphonothioate synthons is described. The 5'-DMT-nucleoside H-phosphonothioate monomers were prepared in two high yielding steps from commercially available phosphoramidites. This strategy for the synthesis of H-phosphonothioate monomers proved versatile and allowed for the synthesis of cholesterol H-phosphonothioate synthons. Synthetic protocols for the assembly of phosphorodithioate DNA using an automated synthesizer were developed. The H-phosphonothioate solid-phase synthesis method facilitates the preparation of oligonucleotide conjugates, as demonstrated by the example of attachment of 5'-cholesterol oligonucleotides. (C) 1999 Elsevier Science Ltd. All rights reserved.