Proton magnetic resonance studies of actinomycin D complexes with mixtures of nucleotides as models for the binding of the drug to DNA

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Abstract
The PMR spectra of actinomycin solutions with mixtures of deoxynucleotides were investigated to determine the relative preference for the binding of guanine and adenine nucleotides to the 2 nucleotide binding sites of actinomycin D. An analysis of the chemical shifts of the actinomycin D resonances shows that adenine and guanine nucleotides competitively bind to the benzenoid portion of the phenoxazone ring of actinomycin D while guanine nucleotides bind stronger than adenine nucleotides to the quinoid portion of the phenoxazone ring. The chemical shift data for the titrations of actinomycin D with pdG-dG, pdC-dC and an equimolar mixture of these complementary deoxydinucleotides show that: pdG-dG forms a stacked complex much like dGMP, pdC-dC does not bind to actinomycin D under the conditions used in these experiments and in the titration of actinomycin D with the equimolar mixture of pdG-dG + pdC-dC, a miniature intercalated complex is formed.

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