Dr. Norma Dunlap - Research Interests

Our primary research interest is in organic synthesis of potentially bioactive compounds. Three synthetic projects are currently underway. The major project is focused on the design and synthesis of cyclopropyl-containing peptidomimetics as potential enzyme inhibitors. An efficient (four step) approach to a core structure has been developed, using protected amino acids as starting materials. The key step involves a sulfur ylide cyclopropantion, and differentiation at three variable points leads to compounds with potential as HIV protease, HCV NS3 protease or BACE inhibitors. In addition to the synthesis of these compounds, we are interested in molecular modeling into enzyme active sites, in collaboration with Dr. Anatoliy Volkov in MTSU's chemistry department. X-ray crystal structures for HIV protease, HCV NS3 protease and BACE are all available from the Protein Data Bank, and proposed peptidomimetics docked into these enzymes will provide insight for optimization of binding interactions.

A second project involves the synthesis of dimers of epi-podophyllotoxin as potential anti-tumors agents, and as tools for the study of the mechanism of topoisomerase. This project has been carried out in collaboration with Prof. Neil Osheroff at Vanderbilt University.

A third project involves a new approach to labeled mevalonolactone, for use in studies of the sterol composition of dinoflagellates. Previous reported syntheses are inefficient, and the new approach offers improved access to this compound. This project is being pursued in collaboration with Prof. Jeff Leblond in MTSU's biology department.

Additionally, we are interested in the isolation and identification of active components of extracts obtained from botanical samples used in traditional Chinese medicine.