Prof. David Wilson, Georgia State University

DNA Minor Groove Interactions of Compounds with Nonclassical Shapes: The Importance of Induced Fit and Bound Water for Strong Interactions

Biochemistry Division Seminar Series

The use of synthetic organic compounds to control key cellular processes and regulate cell function in a desired fashion is a research goal that is central to chemical biology. A particularly exciting feature of the pursuit of this goal involves design, study and development of cell permeable compounds that can selectively recognize nucleic acids and regulate the expression of specific genes and/or DNA replication. For chemists working in this area there is an initial simple question that is not simple to answer: how do we discover, design and develop molecules with the desired properties? A collaborative group of bioorganic/medicinal, biophysical and computational chemists at Georgia State University is approaching this research area with the goal of preparation and study of compounds that selectively target the minor groove of the DNA double helix. A combination of directed synthesis with detailed of biophysical analysis has allowed us to discover a number of interesting and potentially important variations on traditional DNA recognition modes. The classical Watson-Crick DNA minor groove has a uniform structure that can potentially be selectively recognized through the sequence-dependent variation of base pair functional groups in the groove. We now know that sequence-dependent variations in groove structure and solvent interactions occur that could be quite important for specific recognition. We are searching for methods to combine these concepts in the design of relatively small compounds with unique recognition modes. Such compounds can provide important fundamental information on biomolecular interactions and can serve as the basis for new potential therapeutic agents. Correlations between protein and small molecule interaction features will be described.

Supported by NIH, The Gates Foundation, and The Georgia Research Alliance

For more information contact Prof. Yomi Oyelere (404-894-4047).