Synthesis and hybridisation properties of phosphonamidate ester modified nucleic acid

The replacement of the two backbone oxygen atoms of the phosphodiester link age of DNA with carbon and nitrogen in the form of a phosphonamidate eater linkage, in both possible regioisomeric forms, is described. An alkylation reaction with the 3'-C-P-N-5' methyl phosphonamidate regioisomer yielded th e corresponding N-methylated analogues. For each example separation into in dividual phosphonamidate eater diastereoisomers was performed prior to inco rporation into oligonucleotides. The effect upon duplex stability for DNA o ligonucleotides containing each of these modifications with complimentary R NA is reported.