Determining the binding mode of DNA sequence specific compounds

The binding mode of DNA sequence specific compounds can be established by characterizing the binding agents completely. A variety of solution studies may indirectly be used for determining the binding mode. The sequence specificity of certain DNA binding drugs has been found to be related to the specific mode of binding. In this study, only certain methods are found to be reliable to infer the binding mode of DNA binding drugs. Comparative fluorescence and hydrodynamic studies have been done. The results in this study show that most fluorescence measurements are not sensitive indicators of the mode of binding. The fluorescence intensity, fluorescence polarization, and quenching measurements can detect the binding interaction of ligands with DNA. Fluorescence contact energy transfer studies can reliably indicate the different mode of binding. These results illustrate reliable criteria that may be used to distinguish the intercalation from the groove binding. They also infer the mode of binding in the absence of high-resolution structural data. (C) 2001 Elsevier Science Ltd. All rights reserved.