Carston R. Wagner, Ph.D.
Professor and Director of Graduate Studies
Department of Medicinal Chemistry

Education:

B.S., University of North Carolina, 1981
Ph.D., Duke University, 1987
NIH Postdoctoral Fellow, Department of Chemistry, Pennsylvania State University, 1987-1991

Links:

Course: Phar 6153 - Pharmaceutical Immunology
Course: MedC 8700/Chem 8700 - Advanced Concepts in Medicinal Chemistry
Course: Chem 5245/MedC 5245 - Introduction to Drug Design
Course: Phar 6159 - Pharmaceutical Immunology and Recombinant DNA-Derived Drugs
Web site: Chemical Biology Initiative
Web site: Wagner Research Group

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Research Interests:

The multidisciplinary chemical biological research program pursued in my laboratory applies the areas of synthetic chemistry, medicinal chemistry, enzymology, molecular biology, biochemical pharmacology, X-ray crystallography, electron microscopy, molecular modeling and spectroscopy to; 1) the development of new approaches to drug design and delivery, 2) understanding environmental arylamine carcinogen activation and 3) the engineering of protein nanostructures. My group has been interested in the targeted delivery of antiviral and anticancer nucleotides to virally infected or cancer tissues. Our discovery that bacterial and human Histidine Triad Nucleotide Binding Proteins (Hints) are phosphoramidases, has allowed us to rationally design potential therapeutic nucleotide prodrugs that can be targeted to diseased tissues. We are currently applying our understanding to the design of anticancer and antiviral pronucleotides. In addition, we have discovered a unique and exciting biochemical function for these enzymes, which we are characterizing. In another related project, we are designing unique drug like molecules capable of controlling protein translation in cancer cells. Our hope is that we will be able to use these molecules in combination with known anticancer drugs for the development of more effective chemotherapeutic strategies. Our laboratory is also interested in understanding how arylamine N-acetyltransferases activate common environmental carcinogens. We have developed the first detailed understanding of the catalytic mechanism of these important enzymes and, along with collaborators, are pursuing the structure of these enzymes by NMR spectroscopy. Lastly, because they have a high degree of chemical functionality and structural complexity, proteins could be valuable nanotechnology building blocks. We have begun to develop methods to capture this potential with synthetic chemical dimerizers and designed multimeric proteins. We are applying our new found knowledge to the construction of two and three dimensional nanostructures.

Our hope is to use these structures as new scaffolds for the assembly of recombinant antibodies and enzymes.

 Publications:

Chou, Tsui-fen, Cheng, Jilin, Tikh, Ilya B., and Wagner, Carston R., "Evidence that Human Histidine Triad Nucleotide Binding Protein 3 (Hint3) is a Distinct Branch of the Histidine Triad(HIT) Superfamily", Journal of Molocular Biology, 373,4,978-89 (2007)

Chou, Tsui-fen, Sham, Y., and Wagner, Carston R., "The Impact o fthe C-Terminal Loop of Histidine Triad Nucleotide Binding Protein1 (Hint1) on Substrate Specificity", Biochemistry, 45,13074-13079(2007)

Chou, T.-F.; Cheng, J.; Bieganowski, P.; Brenner, C.; and Wagner, C. R., ³¹P NMR and Genetic Analysis Establish hinT as the Only E. coli Purine Nucleoside Phosphoramidase and as Essential for Growth under High Salt Conditions. J. Biol. Chem., 2005, 280, 15356-15361.

 Ghosh, P.;  Park, J.; Peterson, M.;  Bitterman, P. B.,; Polunovsky, V. A.,  Wagner, C. R., Design and Synthesis of 7-Methyl Guanosine Phosphate Analogs as Inhibitors of eIF4E. Bioorg. Med. Chem. Letts, 2005, 15, 2177-2180.

 Wang, H.; Hanna, P. E.,; Wagner, C. R., The Catalyitic Mechanism of Hamster Arylamine N-Acetyltransferase 2. Biochemistry, 2005, 44, 11295-11306

 Carlson, J. T. C.; Jenna, S.;  Flenniken, M.; Chou, T.-F.; Siegel, R,; Wagner, C. R.; Chemically Controlled Self-Assembly of Protein Nanorings.  J. Amer. Chem. Soc., 2006, 128, 7630-7638