ZWITTERIONIC OLIGODEOXYRIBONUCLEOTIDE N3'-]P5' PHOSPHORAMIDATES - SYNTHESIS AND PROPERTIES

Zwitterionic, net neutral oligonucleotides containing alternating nega tively charged N3'-->P5' phosphoramidate monoester and positively char ged phosphoramidate diester groups were synthesized, The ability of zw itterionic phosphoramidates to form complexes with complementary DNA a nd RNA was evaluated, Stoichiometry and salt dependency of these compl exes were determined as a function of the nature of the heterocyclic b ases of the zwitterionic compounds, Unlike the melting temperatures of the natural phosphodiester-containing oligomers, the T-m of the duple xes formed with the zwitterionic oligothymidylates was salt concentrat ion independent, The thermal stability of these duplexes was much high er with Delta T-m values of 20-35 degrees C relatively to phosphodiest er counterparts at low salt concentrations, The zwitterionic oligoaden ylate formed only 2Py:1Pu triplexes with complementary poly(U) or poly (dT) strands, The thermal stability of these complexes was dependent o n salt concentration, Also, the T-m values of the complexes formed by the zwitterionic oligoadenylate with poly(U) were 6-41 degrees C highe r than for the natural phosphodiester counterpart, Triplexes of this c ompound with poly(dT) were also more stable with a Delta T-m value of 22 degrees C at low salt concentrations. Complexes formed by the zwitt erionic oligonucleotides with complementary RNAs were not substrates f or RNase H. Surprisingly, the duplex formed by the all anionic alterna ting N3'-->P5' phosphoramidate-phosphodiester oligothymidylate and pol y(A) was a good substrate for RNase H.