Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 134, Issue 45, Pages 18667-18676Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ja3066368
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Funding
- National Science Foundation [DMR 07-06170, DMR 12-06754]
- National Institutes of Health [R01HG004512]
- Division Of Materials Research
- Direct For Mathematical & Physical Scien [1206754] Funding Source: National Science Foundation
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A variety of solution methods exist for analysis of interactions between small molecule ligands and nucleic acids; however, accomplishing this. task economically at the scale. of hundreds to thousands of sequences remains. challenging. Surface assays offer a prospective solution through array based multiplexing, capable of mapping out the full sequence context of a DNA/ligand interaction in a single experiment However, relative to solution assays, accurate. quantification of DNA/ligand interactions in a surface format must contend with limited understanding of molecular- activities and interactions at a solid liquid. interface. We report a surface adaptation of a solution method in which:shifts,in duplex stability, induced by ligand binding and quantified from melting transitions, are used for thermodynamic analysis of DNA/ligand interactions. The results are benchmarked against solution calorimetric data Equilibrium operation is confirmed through superposition of denaturation/. hybridization transitions triggered by heating and cooling. The antibiotic compound netropsin, which undergoes electrostatic and. sequence specific minor groove interactions with DNA, is Used as a prototypical Small molecule: DNA/netropsin interactions are investigated as a function of ionic strength and drug concentration through electrochemical tracing of surface melt transitions. Comparison with solution values finds excellent agreement in free energy, though reliable separation into enthalpic and entropic contributions proves more difficult The results establish key guidelines for analysis of DNA-ligand interactions via reversible melting denaturation at surfaces.
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