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) backb ones along with segments of internucleotidic O-methylphosphate (POOMe) or O-methylphosphorothioate (PSOMe) linkages have been accomplished u sing N-pent-4-enoyl (PNT) nucleoside phosphoramidite synthons. The T(m )s of the MBOs reveal that they form stable duplexes with complementar y DNA and RNA. The MBOs also showed increased resistance to degradatio n by nucleases. Consequently, the MBOs with methylphosphotriester segm ents represent a novel class of antisense oligonucleotides with potent ial for therapeutic and diagnostic applications. Copyright (C) 1996 El sevier Science Ltd