Understanding ligand-DNA interactions enables the design of new therapeutic compounds and hinges in part on the development of technologies amenable to affordable high-throughput screening of drug candidates. The cost of analyzing drug-DNA interactions on solid supports can be dramatically reduced in comparison to solution assays. In this study, the binding thermodynamics of a small ligand to DNA were analyzed via solid-phase DNA melting-hybridization experiments. DNA �probe� molecules were immobilized on the substrate and immersed in a sample medium containing complementary �target� DNA labeled with an electroactive tag. The extent of probe-target hybridization was monitored as a function of temperature with electrochemical methods. In the presence of a model drug, netropsin, the DNA helix-coil transition was shifted to higher temperature, allowing characterization of thermodynamic parameters of drug binding. Free energies acquired from the surface melting scans were in good agreement with those from solution measurements.

Surface DNA melting and hybridization as diagnostic tool for drug-DNA interactions

243rd National Meeting (2012)

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