SYNTHESIS, BIOPHYSICAL AND BIOLOGICAL EVALUATIONS OF NOVEL ANTISENSE OLIGONUCLEOSIDES CONTAINING DEPHOSPHONO-INTERNUCLEOSIDIC LINKAGES

Efficient large-scale syntheses of methylene(methylimino) (MMI) linked mixed base nucleosidic dimers have been accomplished. These dimers we re successfully incorporated into deoxyoligonucleotides by automated s olid-support synthesis. The hybridization properties, nuclease stabili ty, RNase H mediated cleavage and in vitro biological activity of nove l chimeric oligomers have been studied. The biophysical and biological evaluation of these chimeric oligomers containing MMI Linkages sugges ts that MMI is a promising chemical modification of the backbone linka ge for the construction of antisense molecules useful as therapeutics.