Abstract
When a drug molecule binds to DNA, a number of physical properties change. For example, in the case of both proflavine and actinomycin, there is a red shift of the visible absorption band, and in this respect the two compounds seem similar. However, the time axis provides an additional coordinate for distinguishing reactive processes. Using again the example of proflavine and actinomycin, the two compounds differ by orders of magnitude in their rates of reaction with DNA, and the reaction mechanism for the latter is much more complex than for the former. In both cases, kinetic measurements are able to show that at equilibrium there is a mixture of complex forms, and that static measurements determine only the average complex properties. This, then, is the function of kinetic studies of complex formation: to clarify the mechanism or steps in the binding process, and to separate effects due to different complex forms by utilizing resolution along the time axis. In addition, one may find in some cases that biological activity is correlated strongly with kinetic rather than equilibrium properties of the complex. An example is the actinomycin DNA complex, for which a slow dissociation rate seems essential for biological activity (Müller and Crothers, 1968).
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Crothers, D.M. (1971). Kinetics of Binding of Drugs to DNA. In: Hahn, F.E. (eds) Proceedings of the Research Symposium on Complexes of Biologically Active Substances with Nucleic Acids and Their Modes of Action. Progress in Molecular and Subcellular Biology, vol 2. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-65141-0_2
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DOI: https://doi.org/10.1007/978-3-642-65141-0_2
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