Interaction specificity of the anthracyclines with deoxyribonucleic acid

Abstract

The interaction specificity of salmon sperm DNA with various derivatives of daunorubicin was studied. The results of binding, viscometric, 1H NMR, flow dichroism, DNA template inhibition, rates of dissociation and circular dichroism studies were consistent with an intercalation mode of binding of the anthracycline ring as shown by other investigators. Strength of binding, case of dissociation of DNA-anthracycline complexes and degree of inhibition of DNA-dependent RNA polymerase are dependent on the presence of the amino sugar moiety of daunoseamine. The results are consistent with specific H bonding of the amino group of the sugar moiety with DNA as suggested earlier by Pigram et al. Peptide derivatives substituted at the amino sugar function of daunorubicin lower the affinity of the drug to DNA and interfere with the full insertion of anthracycline drugs between base pairs of DNA. The significance of these findings in relation to the biological efficacy of daunorubicin and related derivatives as antileukemic agents is discussed.