Kinetic studies of actinomycin D binding to mono-, oligo-, and polynucleotides

The kinetics of association of actinomycin D with poly(dG-dC) and the oligonucleotides d-(CGCGCGCG), d(GCGCGC), d(ATGCAT), d(CGCG), and d(GC), as well as with several mononucleotides, have been investigated. In all cases, the association interaction was characterized by several slow, unimolecular processes with qualitatively similar rate constants. The activation enthalpies and entropies for the association of actinomycin with deoxyguanosine 5'-monophosphate resemble closely those typical for calf thymus DNA. This observation of little or no sequence or length dependence in the binding kinetics suggests that the slow phases arise from properties of the drug alone. These results are discussed in terms of both the shuffling model of Fox and Waring [Fox, K.R., & Waring, M.J. (1984) Eur. J. Biochem. 145, 579] and the model of Muller and Crothers [Muller, W., & Crothers, D.M. (1968) J. Mol. Biol. 35, 251] involving both rapidly forming and slowly forming complexes, with the rapidly forming species being the predominant one.