STABILIZATION OF TRIPLE-STRANDED OLIGONUCLEOTIDE COMPLEXES - USE OF PROBES CONTAINING ALTERNATING PHOSPHODIESTER AND STEREO-UNIFORM CATIONIC PHOSPHORAMIDATE LINKAGES

Pyrimidine oligonucleotides containing alternating anionic and stereo- uniform cationic N-(dimethylaminopropyl)phosphoramidate linkages [e.g. d(T+T-)(7)T, d(T+T-)(2)(T+C-)(5)T and (U'+U'-)(7)dT, where U' is 2'-O -methyluridine)] are shown to bind to complementary double-stranded DN A segments in 0.1 M NaCl at pH 7 to form triple-stranded complexes wit h the pyrimidine.purine.pyrimidine motif. For each of the sequences in vestigated, one stereoisomer bound with higher affinity, and the other stereoisomer with lower affinity, than the corresponding all-phosphod iester oligonucleotide, The stereoisomer of d(T+T-)(7)T that interacte d weakly with a dT.dA target in 0.1 M NaCl formed a novel dA.dA.dT tri ple-stranded complex with poly(dA) or d(A(15)C(4)A(15)) in 1 An NaCl; in contrast, the stereoisomer that bound strongly to the dT.dA target failed to form a dA.dA.dT triple-stranded complex.