Kinetic studies of drug-dinucleotide complexes.

Three classes of kinetic behavior are observed in the complexes of actinomycin or ethidium with deoxydinucleotides. First, the initial dinucleotide binding to form a 1:1 complex is a rapid bimolecular process, whose rate could be measured for combination of actinomycin with d(pTpG) d(pGpT), d(pGpA), d(pGpG) d(pCpGpG), and d(pCpG) andfor combination of ethidium with d(pGpC). Second, with one exception, all reactions in which a second dinucleotide is added to form a 2:1 dinucleotide-drug complex are limited by a first-order step at high concentration. This class includes the combination of actinomycin with all dinucleotides tested except d(pGpC), and the reaction of ethidium with nucleotides of complementary sequence pyrimidine-purine, such as d(pCpG). The final class is the special case of d(pGpC) interacting to form a 2:1 complex with actinomycin. Third-order kinetics is observed, with no evidence for a first-order, rate-limiting step.