This proposal for research on "Kinetics and Thermodynamics of Intercalator Binding to psDNA and apDNA" between Dr. Jonathan B. Chaires of the University of Mississippi Medical Center and Dr. Thomas Jovin of the Max-Planck Institute for Biophysical Chemistry, Goettingen, FRG, is sponsored by NSF under the U.S.- Germany Cooperative Research Program. Dr. Chaires plans to pursue fundamental studies of intercalation reactions using instrumentation unavailable to him at his home institution. The interaction of daunomycin (an important anticancer antibiotic) with DNA will be studied by pressure-jump relaxation kinetic methods, in order to explore the mechanism by which the antibiotic locates and binds to its preferred sites within heterogeneous DNA sequences. The thermodynamics of the binding of ethidium bromide and daunomycin to parallel stranded DNA will be studied using steady-state fluorescence methods. Parallel stranded DNA (psDNA) is a novel structural variant of DNA recently discovered in the Jovin laboratory, and consists of a duplex DNA molecule in which the individual strands are in a parallel 3'8822596 Antholine This proposal for research on "Low Frequency ESR Studies of Cu-Cu Interactions" between Dr. William E. Antholine of the Medical College of Wisconsin and Dr. Peter M. H. Kroneck of the Universitaet Konstanz, FRG, is sponsored by NSF under the U.S.-Federal Republic of Germany Cooperative Research Program. This research will attempt to demonstrate the efficiency of low- frequency (S-band) electron spin resonance (ESR) for unravelling the ESR spectra from ESR detectable binuclear copper sites. The researchers will compare ESR data from Cu(1.5)Cu(1.5) sites in N2OR (nitrous oxide reductase), to ESR data from cytochrome oxidase, to determine whether the Cu/a site is a mixed valence binuclear copper site. Analysis of line widths and strain parameters through spectral simulation is expected to account for the shape of these ESR signals. A demonstration of the enhanced sensitivity of the half field lines at S-band for Cu(II)Cu(II) dimers in nitric oxide treated tyrosinase, ceruloplasim, and nitrous oxide reductase will be a useful result, by itself, for copper dimers. The ESR group in Wisconsin has pioneered the use of multifrequency ESR as a prime spectroscopic modality for analysis of Cu(II) sites in biological systems. The group in Konstanz has studied the relationship between structure and function of catalytic centers in multicopper proteins such as ascorbate oxidase and nitrous ovide reductase. Thus, the two groups will complement each other in carrying out the long term goal of the project: to develop techniques to extract physical chemical data from cupric complexes in cells and eventually in animal systems.
