A Novel Methodological Approach for the Analysis of Host-Ligand Interactions

Strat, Daniela; Missailidis, Sotiris and Drake, Alex F. (2007). A Novel Methodological Approach for the Analysis of Host-Ligand Interactions. ChemPhysChem, 8(2) pp. 270–278.

DOI: https://doi.org/10.1002/cphc.200600442

Abstract

Traditional analysis of drug binding data relies upon the Scatch and formalism. These methods rely upon fitting of a linear equation providing intercept and gradient data that relate to physical properties, such as the binding constant, cooperativity coefficients and number of binding sites. However, the existence of different binding modes with different binding constants makes the implementation of these models difficult. This article describes a novel approach to the binding model of host-ligand interactions by using a derived analytical function describing the observed signal. The benefit of this method is that physically significant parameters, that is, binding constants and number of binding sites, are automatically derived by the use of a minimisation routine. This methodology was utilised to analyse the interactions between a noval antitumour agent and DNA. An optical spectroscopy study confirms that the pentacycil acridine derivative (DH208) binds to nucleic acids. Two binding modes can be identified. A stronger one that involves intercalation and a weaker one that involves oriented outer-sphere binding. In both cases the plane of the bound acridine ring is parallel to the nucleic acid bases, orthogonal to the phosphate backbone. Ultraviolet (UV) and circular dichroism (CD) data were fitting using the proposed model. The binding constants and the number of binding sites derived from the model remained consistent across the different techniques used. The different wavelengths at which the measurements were made maintained the coherence of the results.

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