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.

Interceptor effect of C60 fullerene on the in vitro action of aromatic drug molecules

“…These features enable us to draw a parallel with the well-investigated drug-xanthine systems (Buchelnikov et al 2012;Evstigneev et al 2006Evstigneev et al , 2008Evstigneev et al , 2011Evstign eev 2010Evstign eev , 2013Goluriski et al 2013;Larsen et al 1996;Piosik et al 2010;Traganos et al 1991;Woziwodzka et al 2011), for which similar effects are observed on joint in vitro action of aromatic BACs. Of particular importance here is that in the drug-xanthine systems, the operation of the interceptor mechanism (i.e., the drugxanthine hetero-association) can be considered as widely accepted.…”

“…However, the study of such a mechanism is complicated by possible influence from other molecular processes, one of which is most often referred to as a 'protector' mechanism, i.e., the drug/interceptor competition for the binding sites on DNA (Buchelnikov et al 2012;Evstigneev 2010Evstigneev , 2013Evstigneev et al 2011;Goluriski et al 2013). Investigation of the interceptor and protector mechanisms for DNA-bind ing drugs used in combination is the subject of the theory of interceptor/protector action (Buchelnikov et al 2012;Evstigneev et al 2008Evstigneev et al , 2011Evstigneev 2010). Unfortu nately, the applicability of the protector mechanism within the system containing C6fl fullerene cannot be estimated on the basis of the currently available literature data.…”

“…These drugs form stable non-cova lent complexes with C6fl fullerene Evstigneev et al 2013) and were previously characterized as the ligands that follow the mechanism of interceptor/ protector action when used in combination with various types of aromatic interceptor molecules (Buchelnikov et al 2012;Evstigneev et al 2006Evstigneev et al , 2008Evstigneev 2010Evstigneev , 2013Larsen et al 1996;Piosik et al 2010;Traganos et al 1991).…”

General statistical-thermodynamical treatment of one-dimensional multicomponent molecular hetero-assembly in solution

“…[35,36]). Partial derivative of N corr with respect to the monomer concentration C i at C i ¼ 0 extracts from N corr all terms related to complexes containing i-type monomer, whereas the value of N corr at C i ¼ 0 gives the part of N corr not containing the i-type monomer.…”

“…(32) at N ¼ 2 and N ¼ 3 enables one to get N ð1Þ corr identical to those derived in Refs. [35,36]. Detailed derivation of the grand partition function for above-mentioned case is outlined in Appendix D.…”