Tuning the Thermodynamic and Kinetic Properties of the Binding of Hairpin Polyamides to Their Cognate DNA Sequences, through Incorporation of Intercalating and Threading Agents

Hope College, Holland MI

Investigators

Abstract

With this new award the Organic and Macromolecular Chemistry Program supports the work of Professor Moses Lee of the Department of Chemistry at Furman University and Professor W. David Wilson of the Department of Chemistry at Georgia State University. The research will involve the synthesis and characterization of hairpin polyamides that bind to DNA in a sequence specific manner. In order to enhance binding to DNA, the sequence specific hairpin polyamide JH-37, previously developed in the PI's lab, will be modified by the incorporation of pendant intercalating and threading groups. These added groups will be chosen for their preference for binding to the minor groove of DNA. Once these compounds are synthesized, the thermodynamics and kinetics of their binding to DNA will be investigated by surface plasmon resonance. Those compounds that exhibit favorable binding constants and kinetics will be examined further by isothermal titration calorimetry and nuclear magnetic resonance. In this way, rational ligand design and synthesis will be linked to the biophysical properties that determine DNA-ligand interactions. These collaborative studies, which will be carried out by undergraduates, graduate students and postdoctorals, will yield information of importance in development of novel biologically active compounds, specific gene knockouts, and gene based biosensors.