Specificity of Interaction of Pyrimidine Oligonucleotides with DNA at Acidic pH in the Presence of Magnesium Ions: Affinity Modification Study

Abstract

Sequence-specific alkylation of dsDNA with pyrimidine oligonucleotides bearing an alkylating group at the 3' and 5' terminal phosphates, or both, has been investigated. At pH 5.4, sequence-specific modification of guanosines of the DNA in the vicinity of the target purine-pyrimidine sequence occurs. The reactive group at the 5' terminus of the oligonucleotides attacks guanosines in the purine strand of the target DNA. The reactive group at the 3' end can interact with guanosines in both strands of the DNA. Bifunctional reagents can alkylate both strands of the DNA simultaneously. At pH 4 in the presence of magnesium ions, the oligonucleotide derivatives can form imperfect complexes with sequences homologous to the target sequence and alkylate the DNA at the corresponding positions.