Analysis of drug-DNA interactions on solid supports via electrochemical techniques paves the way to multiplexed screening platforms compatible with existing microelectronic technology. In this study, the binding thermodynamics of a model drug to DNA were analyzed via DNA melting-hybridization transitions at solid-liquid interfaces. Surface-tethered DNA �probe� molecules were immersed in a medium containing complementary �target� DNA labeled with an electroactive tag. Electrochemical techniques were used to monitor probe-target hybridization as a function of temperature, leading to generation of hybridization-melting curve. In the presence of a minor groove binding drug, netropsin, DNA helix-coil transition was shifted to higher temperature, indicating ligand-induced stabilization of double-stranded DNA. Analysis of hybridization curves in the presence and absence of netropsin allowed determination of thermodynamic parameters of ligand binding. This approach is also feasible for analysis of covalently binding drugs, e.g. cisplatin, that reduces nucleic acid thermal stability due to disruption of the helical DNA structure.

Drug-DNA binding analysis via DNA melting transitions at solid-liquid interfaces

244th National Meeting (2012)

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