SEARCH FOR DNA-REPAIR INHIBITORS - SELECTIVE BINDING OF NUCLEIC BASESACRIDINE CONJUGATES TO A DNA DUPLEX CONTAINING AN ABASIC SITE

The abasic site is one of the most frequent DNA lesions generated by s pontaneous or enzymatic cleavage of the N-glycosidic bond. The abasic site is also an intermediate in the nucleotide and base excision DNA r epair. We examined molecules which recognize and cleave DNA at the aba sic site with high efficiency. These molecules incorporate in their st ructure a nucleic base for abasic site recognition, an intercalator fo r DNA binding, and a polyamino linker for ionic interaction and DNA cl eavage. Such compounds, by interfering with abasic sites in DNA, are a lso inhibitors of DNA repair. In order to better understand the parame ters of the interaction, we carried out a UV thermal denaturation stud y of synthetic oligonucleotides containing the lesion both in the abse nce and in the presence of the drugs. A similar study was also carried out using the corresponding nonmodified oligonucleotide. The results indicate selective binding of the base-chain-intercalator conjugates t o the abasic site containing oligonucleotides.