Graduated in 1978 at the University of Connecticut (Professor Gerson Kegeles, mentor) NIH Postdoctoral Fellow, Yale University, 1979-1981 (Professor Donald Crothers, mentor). Physical biochemistry of nucleic acids and their interactions. A complete understanding of the mechanism of gene expression requires knowledge of the physical chemistry of the structural transformations and molecular interactions of the nucleic acids. Our laboratory studies conformational transitions in DNA and the binding of a number of medically important small molecules to DNA, using the methods of both physical biochemistry and molecular biology. Our laboratory is superbly equipped for biochemical spectroscopy, with state-of-the-art instrumentation for UV/visible absorption spectroscopy, circular dichroism and both steady-state and time-resolved fluorescence spectroscopy. In addition, we use differential scanning microcalorimetry for a rigorous thermodynamic characterization of nucleic acid conformational transitions and microtitration calorimetry for the direct determination of ligand binding enthapies. Specific studies currently under investigation are: (1) energetics of anthracycline antibiotic binding to DNA; (2) mechanism of allosteric interactions of anti biotics with DNA; and (3) rapid screening of structural selectivity of DNA binding agents. Recent Publications Spink, C. and Chaires, J.B. The efficts of hydration, ion release and excluded volume on the melting of triplex and duplex DNA. Biochemistry 38:496-508, 1999. Bailly, C., Qu, X., Graves, D. E., Prudhomme, M., and Chaires, J.B. Calories from carbohydrates. Energetic contributions of the carbohydrate moiety of rebeccamycin to DNA binding and the effect of its orientation on topoisomerase I inhibition. Chemistry & Biology 6: 277-286, 1999 Qu, X. and Chaires, J.B. Analysis of drug-DNA binding data. Methods in Enzymology, Numerical Computer Methods Part C, 321: in press, 1999 Qu, X. and Chaires, J.B. Contrasting hydration changes of ethidium and daunomycin binding to DNA. Journal of the American Chemical Society (Communication) 121: 2649 - 2650, 1999 Leng, F., Priebe, W. and Chaires, J. B. Ultratight binding of a new bisintercalating anthracycline antibiotic. Biochemistry 37: 1743 - 1753, 1998. Chaires, J. B. Energetics of drug-DNA interactions. Biopolymers 44: 201 - 215, 1997. PATENTS Priebe, W., Chaires, J. B., Przewloka, T., Fokt, I., and Perez-Soler, R. Bis-anthracyclines with high activity against doxorubicin resistant tumors. United States Patent Number 5,874,412, Date of Patent: February 23, 1999