Abstract

The interactions of small molecules with nucleic acids have provoked considerable interest in the field of anticancer drug design over the past three decades; however, critical information linking the physical-chemical properties associated with these complexes with their biological effectiveness remains unclear. Significant progress has been made towards unraveling the structural and dynamic properties of many ligand-DNA complexes which has provided pivotal insight into the design and development of more effective second and third generation chemotherapeutic agents for the successful treatment of many types of cancer. Interactions of ligands with DNA are studied by a variety of physical and biochemical methods in an effort to determine the chemical and physical basis of novel binding phenomena such as DNA base sequence selectivity, correlation of structure-activity relationships, linkages between the geometry and thermodynamic properties describing drug-DNA complexes, and influences of substituent modifications on the physical, chemical, and biological properties of the drug-DNA complex.