An efficient synthesis of the novel nucleic acid analogs oligodeoxyrib
onucleotide N3'-->P5' phosphoramidates, where the 3'-oxygen is substit
uted by a 3'-nitrogen, is described, Synthesis of the title compounds
was accomplished by the following synthetic steps, First, 5'-O-DMT bas
e-protected-3'-amino-2',3'-dideoxynucleosides were prepared, The 3'-am
inopyrimidines were obtained via the corresponding 2,3'-anhydronucleos
ides, whereas 3'-aminopurines were derived via 2'-deoxyxylo precursors
, Second, using the prepared 3'-aminonucleosides, oligonucleotide N3'-
->P5' phosphoramidates were synthesized on a solid support, Oligonucle
otide chain assembly was based upon a carbon tetrachloride-driven oxid
ative coupling of the appropriately protected 3'-aminonucleosides with
the 5'-H-phosphonate diester group, resulting in the formation of an
internucleoside phosphoramidate link, Fully deprotected oligonucleotid
e N3'-->P5' phosphoramidates were characterized by ion exchange and re
versed phase HPLC, capillary and slab gel electrophoresis and by P-31
NMR analysis, Oligonucleotide N3'-->P5' phosphoramidates form remarkab
ly stable duplexes with complementary RNA strands and also with themse
lves, where the melting temperature of the complexes exceeded that for
the parent phosphodiester compounds by 26-33 degrees C, Additionally,
duplexes formed by oligonucleotide phosphoramidates with single-stran
ded DNA were also more thermally stable than those formed by phosphodi
esters, The described properties indicate that these compounds may hav
e great potential in oligonucleotide-based diagnostics and therapeutic
applications.