General analysis of competitive binding in drug–interceptor–DNA systems

Abstract

A general model of competitive binding in drug-interceptor-DNA systems has been developed in order to quantify both the interceptor and protector mechanisms. The model involves full parameterization of the basic equations governing the mutual competition between drugs binding to DNA and incorporates as partial cases various similar models existing in the literature. The generality of the model results from strict accounting of the statistical effects of the binding of the drug and interceptor with DNA according to the McGhee-von Hippel formalism, and to the strict treatment of hetero-association between the drug and interceptor, which includes formation of all possible types of self- and hetero-complexes in solution. Indirect experimental evidence is provided for the importance of the protector mechanism in drug-caffeine-DNA systems, which is sometimes ignored in the literature because of the small magnitude of the CAF-DNA binding constant.