Antitumor activity at the molecular level: binding modes in anthracycline–dinucleotide complexes as determined by optical titration and magnetic circular dichroism

Abstract

The first application of magnetic circular dichroism (mcd) spectroscopy to drug–dinucleotide binding is reported. The mcd spectra have been recorded for complexes of the intercalating anthracyclines carminomycin, marcellomycin, and aclacinomycin with the dinucleotide CpG. Analysis indicates that drugs having OH groups peri to each anthraquinone carbonyl (i.e. carminomycin and marcellomycin) bind with only one drug molecule in the central hydrophilic region of the nucleotide. By contrast, aclacinomycin, in which one of the anthraquinone carbonyls lacks a peri-OH, is found to cooperatively bind, and has two drug molecules present in the dinucleotide cavity. The cooperativity of binding has been elucidated via an optical titration procedure.