N. Mignet et Sm. Gryaznov, ZWITTERIONIC OLIGODEOXYRIBONUCLEOTIDE N3'-]P5' PHOSPHORAMIDATES - SYNTHESIS AND PROPERTIES, Nucleic acids research, 26(2), 1998, pp. 431-438
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.