SOLID PHASE METHODS FOR THERMODYNAMIC AND KINETIC QUANTIFICATION OF INTERACTIONS BETWEEN NUCLEIC ACIDS AND SMALL MOLECULES
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United States of America Patent
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Nov 22, 2012
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May 17, 2012
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May 18, 2011
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Abstract
Methods for analysis of interactions between nucleic acid-binding agents (BAs) and nucleic acids (NAs) by performance of nucleic acid denaturation assays on solid supports. Typically, BA is a small molecule less than 1000 g/gmol in molecular weight. The methods provide quantitative thermodynamic and kinetic analysis of BA-NA interaction; for example, in the form of free energies, enthalpies, and entropies of BA-NA binding in case of thermodynamic analysis, or in the form of rate constants and activation energies of BA-NA binding in the case of kinetic analysis. Examples of BAs of interest include transcription regulators and other NA-recognition molecules such as dyes and drug potentiators, DNA-targeted therapeutic agents including anticancer, antibiotic, antiviral, and antitrypanosomal compounds, carcinogens, and any other molecules whose interaction with DNA may, or is suspected to, lead to a biologically-relevant consequence. BA may bind to NA either through physical interactions or through formation of covalent adducts.
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