Exploring the binding of resveratrol to a promoter DNA sequence d(CCAATTGG)2 through multispectroscopic, nuclear magnetic resonance and molecular dynamics studies

Abstract

We report the interaction of resveratrol with an octamer DNA sequence d(CCAATTGG)2, present in the promoter region of many oncogenes, using a combination of absorption, fluorescence, calorimetric and nuclear magnetic resonance techniques to probe the binding. Resveratrol binds to the duplex sequence with a binding constant 2.20 × 106 M−1 in absorption studies. A ligand-duplex stoichiometry of 2.2:1 was obtained with binding constant varying from 103 to 104 M−1 in fluorescence titration measurements. Spectral changes indicated external binding of resveratrol to duplex DNA. Circular dichroism data displayed minimal variation suggesting external binding. Melting temperatures of DNA and its 1:1 complex showed a difference of approximately 2.25 °C, supporting the external binding. Nuclear magnetic resonance data showed resveratrol binds to the minor groove region near the AT base pair from the nuclear Overhauser effect spectroscopic cross peaks. Distance restrained molecular dynamics was employed in explicit solvent condition to obtain the lowest energy structure. The complex was stable and retained the B DNA conformation. Findings in this study identify resveratrol as a minor groove binder to the AT region of DNA and pave the way for exploring resveratrol and its analogues as promising anticancer/antibacterial drug.