The interaction of adriamycin and adriamycin analogues with nucleic acids in the B and A conformations

Abstract

The reinforced intercalative binding to DNA typical of adriamycin and daunomycin can still occur if there is epimerisation at C4′ or if the O-methyl group is lost or if the 9-substituents are deleted or if the 4′-hydroxyl group is lost. In the latter two cases however, there is a reduction in affinity for the DNA, supporting the suggested role of the 9-hydroxyl and 4′-hydroxyl groups in secondary stabilization of the complex. Epimerisation at C-1′ or at C-3′ alters but does not abolish the intercalative mode of binding to DNA whereas epimerisation at C-7 precludes intercalation of the chromophore into the helix of DNA. In contrast to the interaction with the B-form found in DNA, the parent drugs do not intercalate into nucleic acids possessing the A-conformation and none of the above-mentioned structural changes will allow intercalation into A-form nucleic acids.