Michael McNeil

Faculty Microbiology, Immunology, and Pathology

310a Micro

970-491-2506

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About Michael

Our major research goal is the development of new drugs against M. tuberculosis. Our target for new drugs is the unique cell envelope of mycobacteria. The research is proceeding on both an applied and a basic research track. On the applied track we are screening for inhibitors enzymes essential for M. tuberculosis cell wall synthesis, namely the enzymes that form dTDP-rhamnose, UDP-Galf, and UDP-GlcNAc. These inhibitors are tested for their ability to kill M. tuberculosis cells growing in culture and supplied to collaborators to incorporate into crystal structures of the relevant enzymes and to a medicinal chemist collaborator to make addition compounds. Compounds that do well against M. tuberculosis in culture are then tested in mice by Dr. Lenaerts of this department. On the basic research side we are studying the sugar transferases that use the sugar nucleotides above to build the cell wall as well as the enzymes that form the arabinofuranose residues of the cell wall.

Education

PhD, University of Colorado, 1984MS, Massachusetts Institute of Technology, 1972BS, Allegheny College, 1969

Publications

Fang, M. H., R. D. Toogood, A. Macova, K. Ho, S. G. Franzblau, M. R. McNeil, D. A. R. Sanders, and D. R. J. Palmer . 2010. Succinylphosphonate Esters Are Competitive Inhibitors of MenD That Show Active-Site Discrimination between Homologous alpha-Ketoglutarate-Decarboxylating Enzymes. Biochemistry 49:2672-2679. Crick, D., Chatterjee, D., Scherman, M.S., and McNeil, M., Structure and Biosynthesis of the Mycobacterial Cell Wall. In Comprehensive Natural Products II Chemistry and Biology;Mander, L., Lui, H.-W., Eds.; Elsevier: Oxford, 2010; 6: 381–406 .Sivendran, S., Jones, V., Sun, D., Wang, Y., Grzegorzewicz, A. E., Scherman, M.S., Napper, A.D., McCammon J.A., Lee, R. L., Diamond S.L., and McNeil, M. 2010. Identification of triazinoindol-benzimidazolones as nanomolar inhibitors of the Mycobacterium tuberculosis enzyme TDP-6-deoxy-D-xylo-4-hexopyranosid-4-ulose 3,5-epimerase (RmlC). Bioorganic & Medicinal Chemistry 18: 896-908.

                
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