An NMR study of the interaction of daunomycin with dinucleotides and dinucleoside phosphates

The mode of action of the widely used anticancer drug daunomycin was studied by 360 MHz and 100 MHz proton NMR. Information obtained from scalar coupling constants indicates that the conformation of the A ring of the aglycone moiety of daunomycin is maintained upon binding to dinucleotides but that the conformation of the daunosamine ring moiety is altered upon binding. Ring-current-induced chemical shifts of the drug protons were observed as the drug was titrated with deoxydinucleotides. The chemical shift results that daunomycin forms 1 : 1 complexes with deoxydinucleotides and that the strength of the drug-nucleotide interaction is dependent upon the base composition of the dinucleotide. On the basis of the NMR data, a model for the drug/deoxydinucleotide complex is presented featuring intercalation of the drug between the bases of the dinucleoside.