Sequence-specific interaction of pyrimidine oligonucleotides with double-stranded DNA at acidic pH complexes of different types

The interaction of pyrimidine oligonucleotides (OLN₁₅ and OLN₆) and their alkylating derivatives bearing 4-(3-amino)propyl-N-methyl and N-2-chloroethyl (RCl) aniline residues at the 5′-phosphate with a fragment of the human γ-interferon gene was studied. In the presence of 150 mM NaCI at pH 5.4, the yield of dsDNA alkylation was 60% for RCl-OLN₁₅ and 10% for RCl-OLN₆; at pH 4.0 in the presence of 150 mM NaCI and 10 mM MgCl₂, the yield of the dsDNA modification product was 100% for RCl-OLN₆ and 50% for RCl-OLN₁₅. It was shown by native electrophoresis that OLN₁₅ could form with the target dsDNA complexes of two types in the presence of magnesium ions at pH 4.0. One of the complexes was stable at pH 5.4 in the presence of magnesium ions, whereas the other was not. We found that only the complex stable in 10 mM Mg(OAc)₂, pH 5.4, was effectively alkylated.