The long term objectives of this research are to apply the most modern methods of magnetic resonance to the solution of problems in biophysics, biophysical chemistry, pharmacology, and medicine. This proposal will provide a new instrument capable of performing triple resonance experiments in high resolution on solid or semisolid samples employing the methods of magic angle spinning and cross polarization or double cross polarization while decoupling the abundant proton spins. This spectrometer and the very powerful methodology associated with it will be applied to examinations of local dynamics in model compounds mimicking components of proteins, to protein systems, to polynucleotides, to metalolloenzyme systems where the metal environment dynamics will be investigated, to platinum binding to nucleotides, to characterization of platinum binding in tissue preparations, and to mechanistic questions about cyclophosphoramide metabolism and function as an antitumor drug. In addition electron nuclear spin coupling will be investigated as a means for obtaining very dramatic improvements in signal to noise.
