Mode of DNA Binding of Bis-Benzimidazoles and Related Structures Studied by Electric Linear Dichroism

The binding mode of a series of bis-benzimidazole analogues of Hoechst 33258 to a variety of DNAs and polynucleotides has been investigated by electric linear dichroism. Two groups of compounds were examined: (i) benzoxazole and pyridoimidazole derivatives and (ii) pyridoimidazole analogs substituted with an N-alkoxyalkyl group either directed towards the minor groove or directed away from the minor groove. The ELD data indicate that the mode of binding of these drugs varies significantly with the sequence of the target DNA sequence. The DNA binding properties of these drugs are related to their topoisomerase inhibitory properties.