This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).
The goal of this project is to synthesize and evaluate novel small inhibitory molecules of group-1 neuraminidase enzymes. The inhibitors are based on benzoic and nicotinic acid cores that are commercially available. The proposed inhibitors have been validated using computer docking experiments. The ensuing syntheses will be completed using traditional and microwave-assisted organic synthesis methods. Once completed, the biochemical effectiveness and mechanisms of these molecules will be studied. Neuraminidase assays will be performed using purified human Influenza A virus. These assays will utilize 4-methylumbelliferyl-N-acetyl-alpha-D-neuraminic acid which liberates highly fluorescent 4-methylumbelliferone upon hydrolysis. The binding characteristics of these inhibitors will be compared with those of oseltamivir carboxylate (Tamiflu), a known inhibitor.
With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Professors Jeffrey A. Turk and Joe D. Beckmann at Alma College. The combined research of these professors focuses on the understanding of how small molecules interact with the apo-form of the neuraminidase active site. Their research may ultimately lead to the discovery of more efficient inhibitors that are selective towards N1 neuraminidase, which is found on the surface of the highly virulent H5N1 avian influenza virus. This project also provides additional learning opportunities outside synthetic organic chemistry for the undergraduate students involved.
