Binding Study of Berenil and d(CGCGAATTCGCG)2 and d(CGCAAATTTGCG)2 DNA Dodecamers by Isothermal Titration Calorimetry and Molecular Docking Simulations

Berenil, an anti-trypanosomal agent, is a dicationic bis-benzamidine that has been classified as a minor groove binding ligand in AT-rich regions of DNA. However, previous studies have suggested that berenil can bind to various DNA double strands exhibiting both intercalative and minor groove binding modes. In this work we present a biophysical study analyzing the interaction between berenil and two synthetic DNAs that suggests that this molecule shows a mixed bind behaviour when binding to double stranded DNA. It is possible that more than one berenil molecule can bind to DNA dodecamers double strands. The second molecule may be interacting through intercalation. The data from isothermic calorimetric titrations at 298 K were analyzed by Wiseman Isotherm and classical thermodynamic equations. Thermodynamic parameters for complexation between the two DNAs were obtained by ITC experiments and Autodock calculations. The results show that the intercalative effect of the molecule is entropically driven.