Interaction of an anthracycline disaccharide with ctDNA: Investigation by spectroscopic technique and modeling studies

This study was designed to examine the interaction of an anthracycline disaccharide, 4'-O(beta-L-oleandrosyl) daunorubicin (DNR-D2), with calf thymus deoxyribonucleic acid (ctDNA) by UV-vis in combination with fluorescence spectroscopy and molecular modeling techniques under physiological conditions (Britton-Robinson buffer solutions, pH 7.4). By the analysis of UV-vis and fluorescence spectrum, it was observed that the binding mode between DNR-D2 and ctDNA might be intercalation, and fluorescence quenching mechanism of DNR-D2 by ctDNA was a static quenching type. Upon binding to ctDNA, the anthraquinone chromophore of DNR-D2 could slide into the C-G rich region of ctDNA. Hydrogen bonding forces may play an essential role in the binding of DNR-D2 to ctDNA. Furthermore, the results obtained from computational modeling corroborated the experimental results obtained from spectroscopic investigations. These studies are valuable for a better understanding the datailed mode of DNR-D2-DNA interaction, which should be important in deeper insight into the therapeutic efficiency of DNR-D2. (C) 2010 Elsevier B.V. All rights reserved.