The purpose of this work is to study the interactions of DNA with drugs and proteins to elucidate the mechanisms by which DNA function is controlled. Fundamental studies of drug-DNA complexes will include examination of the base sequence-dependence of DNA distortion when drugs are bound, comparative study of the complex of drugs with DNA and chromatin subunits, and study of the effect of drug binding on internal motion in DNA. Methods to be used include transient electric dichroism, relaxation kinetics, triplet-triplet spectroscopy and 31P NMR. Objectives in the study of structural and thermodynamic properties of chromatin will include examination of the size and shape of a variety of multinucleosomes, fluorescence energy transfer experiments to determine the number of base pairs per turn of DNA around a nucleosome, and experiments on the thermodynamics of the interactions that stabilize nucleosomes and spacerless dinucleosomes. Work will continue toward the objective of producing polymeric drugs which are specific for binding to chosen DNA base sequences.