Association of Actinomycin D and Deoxyribodinucleotides as a Model for Binding of the Drug to DNA

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RESUMO

The association of actinomycin D and eleven different deoxyribodinucleotides were studied as model complexes for the interaction of actinomycin D and DNA. All of the deoxyribodinucleotides containing guanine will complex with actinomycin D, and the guanine base has a preferred orientation with respect to the chromophore of actinomycin D. The spectrophotometric binding curve for pdG-dC is sigmoidal (Hill constant = 2.0 ± 0.2), while the binding curves of all other dinucleotides of the form pdN-dG are hyperbolic. The equilibrium expression for the complex with pdG-dC was second order in dinucleotide concentration, with KApp = 1.7 × 107 liter2/mol2, while the binding of pdC-dG was first order in dinucleotide concentration, with KApp 1.8 × 103 liter/mol. The sigmoidal pdG-dC binding curve shows that actinomycin D has a preference for G-C sequences of DNA as potential binding sites.

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