Synthesis, biophysical properties, and stability studies of mixed backbone oligonucleotides containing segments of methylphosphotriester internucleotidic linkages

The synthesis of mixed-backbone-oligonucleotides (MBOs) (15 to 25-mers) which contain phosphoric diester (PO) or phosphorothioate (PS) backbones along with segments of internucleotidic O-methylphosphate (POOMe) or O-methylphosphorothioate (PSOMe) linkages have been accomplished using N-pent-4-enoyl (PNT) nucleoside phosphoramidite synthons. The Tms of the MBOs reveal that they form stable duplexes with complementary DNA and RNA. The MBOs also showed increased resistance to degradation by nucleases. Consequently, the MBOs with methylphosphotriester segments represent a novel class of antisense oligonucleotides with potential for therapeutic and diagnostic applications.