INTERACTION OF ADRIAMYCIN AND ADRIAMYCIN ANALOGS WITH NUCLEIC-ACIDS IN THE B-CONFORMATION AND A-CONFORMATION

The reinforced intercalative binding to DNA typical of adriamycin and daunomycin [antitumor agents] 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 2 cases, 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-metnioned structural changes will allow intercalation into A-form nucleic acids.