6-azacytidine binding to DNA molecules

Abstract

The work is dedicated to experimental study of interactions between biologically active ligand namely 6-azacitidine (6AZC) and DNA molecules. The work is carried out by a combination of spectrophotometric titration in Vis and UV regions and numerical calculations of parameters of binding in ligand-DNA systems. Two types of mixtures are considered: 6AZC-DNA and 6AZC - DNA - EB. The parameters of 6AZC binding to DNA matrixes were obtained by fitting the experimentally obtained titration curves by appropriate theoretical models using optimization programs (DALS, COMP and DALSMOD). The chosen optimal models are the ones giving the best conformity of the calculated intensities of absorption of the study mixture at several wave lengths to the ones obtained experimentally. Another criterion for selection of the optimal model is the minimal value of the Hamilton's factor. The parameters of binding that are calculated with help of the models include association constants, binding site size, molar extinction coefficients etc.The binding parameters in the 6AZC-DNA systems were calculated by the DALS program. It was shown that 6AZC interacts with native and partially damaged DNA molecules. The binding parameters in the 6AZC - DNA - EB mixture were determined by COMP and DALSMOD programs. The highest value of binding constant was found to be for the mixture 6AZC - DNA - EB.