Multivariate investigation of interaction between porphyrin ligands and human telomeric DNA

Abstract

G-quadruplexes are formed by association of DNA strands containing multiple contiguous guanines. The capability of drugs to induce formation or stabilize G-quadruplexes is an active area of cancer therapy investigation. We evaluated interaction between two cationic tetrapyridinoporphyrazines with Na+ and K+ forms of human telomeric G-quadruplex DNA by chemometrics method. An antiparallel quadruplex structure was found to be stabilized more greatly by these two isomers in the presence of K+ and Na+ ions. Equilibrium model of a ligand binding with DNA oligomer has been considered as a process of small molecule adsorption on to a lattice of multiple binding sites. In multivariate analysis methods, it is accounted this assertion that during saturation of the macromolecule by a ligand should expect effect of cooperativity due to changes in DNA conformation or the mutual influence between bound ligands. Such phenomenon cannot be entirely described by the classical stepwise complex formation model. From the results of absorption and circular dichroism measurements, the unique site for the ligand binding is suggested to be the intercalating in guanine tetrad plane quadruplex. We found a 2:1 binding stoichiometry for both ligands and Tel22.