It is now well established that a wide range of important therapeutic drugs exert their effects by binding to DNA. These compounds generally interfere with the actions of many vital enzymes and protein factors involved in DNA metabolism. However, a major limiting factor that exists with the use of these drugs is the occurrence of deleterious side effects.
The McKnight research group is currently involved in the study of novel drug molecules binding to DNA using calorimetric, spectrophotometric, fluorometric and electrophoretic gel-based techniques. The long term goal is to develop a fundamental understanding of drug-DNA interactions and to use this knowledge as a guide to rationally design less toxic therapeutics.
Publications and Professional Activities
- McKnight, R.E., Jackson, D.R. and Yokoyama, K., Temperature Dependence of Congo Red Binding to Amyloid Beta 12-28 , Eur. Biophys. J. 2013, 42 (6), 495-501.
- McKnight, R.E., Insights into the Relative DNA Binding Affinity and Preferred Binding
Mode of Homologous Compounds Using Isothermal Titration Calorimetry (ITC). (Book Chapter) In: Applications of Calorimetry in a Wide Context - Differential Scanning Calorimetry, Isothermal Titration Calorimetry and Microcalorimetry, Elkordy, A.A., Ed, InTech, 2013, ISBN 978-953-51-0947-1.
- McKnight, R.E., Reisenauer, E., Pintado, M.V., Polasani, S.R. and Dixon, D.W., Substituent effect on the preferred DNA binding mode and affinity of a homologous series of naphthalene diimides, Bioorg. Med. Chem., Lett., 2011, 21 (14), 4288-4291.
- Yokoyama, K., Fisher, A.D., Amori, A. R., Welchons, D., and McKnight, R.E., Spectroscopic and Calorimetric Studies of Congo Red Dye-Amyloid Beta Peptide Complexes, J. Biophys. Chem., 2010, 1 (3), 153-163.
- McKnight, R.E., Onogul, B., Polasani, S.R., Gannon, M.K. II, and Detty, M.R., Substituent Control of DNA Binding Modes in a Series of Chalcogenoxanthylium Photosensitizers as Determined by Isothermal Titration Calorimetry and Topoisomerase I DNA Unwinding Assay, Bioorg. Med. Chem., 2008, 16 (24), 10221-10227.
- McKnight, R.E., Ye, M., Ohulchanskyy, T., Sahabi, S., Wetzel, B.R., Wagner, S.J., Skripchenko, A. and Detty, M.R., Synthesis of Analogues of a Flexible Thiopyrylium Photosensitizer for Purging the Blood-Borne Pathogens and Binding Mode and Affinity Studies of their Complexes with DNA, Bioorg. Med. Chem., 2007, 15 (13), 4406-4418.