Properties of triple helix formation with oligodeoxyribonucleotides containing 8-oxo-2'-deoxyadenosine and 2'-modified nucleoside derivatives.

The ability of homopyrimidine oligonucleotides containing 8-oxo-2'-deoxyadenosine (dAOH), 2'-methoxyuridine (Um), 2'-fluorouridine (Uf), 2'-methoxycytidine (Cm), and 2'-fluorocytidine (Cf) to form stable, triple-helical structures with sequences containing the recognition site for the class II-S restriction enzyme, Ksp632-I, was studied as a function of pH. The 8-oxo-2'-deoxyadenosine substituted oligomers were shown to bind within the physiological pH range in a pH-independent fashion, without a compromise in specificity. In particular, the substitutions of three deoxycytidine residues with 8-oxo-2'-deoxyadenosine showed higher endonuclease inhibition than the substitution of either one or two deoxycytidine residues with 8-oxo-2'-deoxyadenosine. In contrast, the oligonucleotides containing 2'-modified nucleosides (Uf, Um, Uf-Cf, Um-Cm, dAOH-Uf, and dAOH-Um) bind in a pH-dependent manner to the target duplex.