We propose to study the structures, binding affinities and dissociation kinetics of drug-nucleic acid complexes, focusing mainly on the anthracycline and actinomycin classes of drugs because of their importance as potential anti-cancer agents. Our objectives are: to elucidate the structures of the drug-nucleic acid complexes, to elucidate and predict base and sugar specificities of drugs, to determine the relative affinities and dissociation kinetics of the above class of drugs and their analogs, and to determine the strand breaking ability of these drugs. By investigating the effect of these drugs on DNA both in vitro and in cells, we hope to understand their biological activity in terms of molecular interactions. To elucidate the structures of these complexes, we will employ various NMR techniques. Base, sugar and sequence specifities in both binding affinities and reaction kinetics will be studied by NMR, absorption and fluorescence spectroscopy. Finally, the ability of these drugs to induce DNA strand breaks will be analyzed by viscoelastometry.