Mixed backbone oligonucleotides containing internucleotidic primary phosphoramidate linkages

Mixed backbone oligonucleotides (MBOs) which contain segments of primary phosphoramidate linkages (PO-NH2) in conjunction with either phosphoric diesters (PO), or phosphorothioates (PS) were prepared. Thermal denaturation of the duplexes with RNA and DNA reveal that they form stable duplexes which display cooperative melting profiles. Preliminary stability studies reveal that the PO-NH2 linkage is resistant to serum nucleases. Thus, these MBOs represent novel antisense molecules.