Association of actinomycin D and deoxyribodinucleotides as a model for binding of the drug to DNA

Abstract

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 K(App) = 1.7 x 10(7) liter(2)/mol(2), while the binding of pdC-dG was first order in dinucleotide concentration, with K(App) 1.8 x 10(3) 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.