Functional Application Areas

DSC and Nucleic Acid-Drug Interactions

DSC provides information on the interactions between DNA and drugs, including: correlation between thermodynamic parameters and solutions structure for the interaction of minor groove ligands with an AAATT/AATTT sequence in DNA (Renzeperis et al, 1995), thermodynamics of DNA-cisplatin and DNA-transplatin (Hofr and Brabec, 2001), study of a bifuntional polymer platinum compound crosslinked to DNA (Hofr et al, 2001), and formation of drug-DNA complexes (Leng, et al, 1999)

Effect of adding ethidium bromide to herring DNA. DNA (1.1 mM) in 6 mM Na2HPO4, 2mM NaH2PO4, 1mM EDTA, pH 7.0, in the absence (scan 1) and presence (scan 2) of 0.5 mM ethidium bromide. Scans were performed in the VP-Capillary DSC at 200° C/hour. DSC data shown are after buffer-buffer reference scan subtraction and concentration normalization. Binding constant estimated to be 1.6 x 104 M-1. DNA samples prepared by Dr. J.B. Chaires, University of Mississippi (currently at University of Louisville)

Abstract: Nucleic acids are common targets for antiviral, anticancer and antibiotic drugs.  DNA-binding drugs are designed to modulate gene activity, and RNA-binding drugs inhibit protein translation.  In order to optimize the efficacy of drugs, as well as discover new drugs, it is important to fully characterize the drug-nucleic acid interaction, including sequence recognition, structural details and the thermodynamics of binding.  This note reviews the use of calorimetry to study the thermodynamics of drug-nucleic acid binding. 

References

Thermodynamic characterization of the multivalent binding of chartreusin to DNA.
Barcelo, F., Capo, D., and Portugal, J.
Nucleic Acids Res 30, 4567-4573 (2002)

Molecular recognition of DNA by small molecules: AT base pair specific intercalative binding of cytotoxic plant alkaloid palmatine.
Bhadra, K., Maiti, M. and Kumar, G. S.  
Biochim Biophys Acta 1770, 1071-1080 (2007)

Energetic basis of molecular recognition in a DNA aptamer.
Bishop, G. R., Ren, J., Polander, B. C., Jeanfreau, B. D., Trent, J. O., and Chaires, J. B.  
Biophys Chem 126, 165-75 (2007)

Parsing free energies of drug-DNA interactions.
Haq, I., Jenkins, T. C., Chowdhry, B. Z., Ren, J., and Chaires, J. B.
Methods Enzymol 323, 373-405 (2000)

Calorimetric techniques in the study of high-order DNA-drug interactions.
Haq, I., Chowdhry, B. Z., and Jenkins, T. C.
Methods Enzymol 340, 109-149 (2001)

Thermal and thermodynamic properties of duplex DNA containing site-specific interstrand cross-link of antitumor cisplatin or its clinically ineffective trans isomer.
Hofr, C. and Brabec, V.
J. Biol. Chem. 276, 9655-9661 (2001) 

Thermodynamic properties of duplex DNA containing a site-specific d(GpP) intrastrand crosslink formed by an antitumor dinuclear platinum complex.
Hofr, B., Ferrell, N., Brabec, V.
Nucleic Acids Res. 29, 2034-2040 (2001)

Ultratight DNA binding of a new bisintercalating anthrocycline antibiotic.
Leng, F., Priebe, W., Chaires, J.B.
Biochemistry 37, 1743-1753 (1999)

Interaction of minor groove ligands to an AAATT/AATTT site: Correlation of thermodynamic characterization and solution structure.
Renzeperis, D., Marky, L.A., Dryer, T., J., Geierstanger, B.H., Pelton, J.G., Wemmer, D.E.
Biochemistry 34, 2937-2945 (1995)

Reference List

DSC – Nucleic Acid-Small Molecule Interactions Reference List

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