James C. Powers Regents' Professor Office: 3308 IBB Phone: 404-894-4038 Fax: 404-894-7452 E-mail James C. Powers Research Group Web site

B.S., Wayne State University, 1959; Ph.D., Massachusetts Institute of Technology, 1963; Special NIH Fellow, University of Washington, 1967.

Georgia Section ACS Herty Medal - 2000; Georgia Tech Distinguished Professor, Highest Academic Award -1999

Research Interests

Dr. Powers is interested in the study of enzyme active sites and the mechanism of enzyme catalysis. New classes of synthetic inhibitors are being designed and synthesized for proteolytic (protein degrading) enzymes of therapeutic importance. Both mechanism-based (or suicide) and transition-state inhibitors are being developed. One area of active research is the design and synthesis of inhibitors for proteases such as caspases and calpain. Inhibitors for calpain, a cysteine protease involved in neurodegeneration, have potential therapeutic utility for the treatment of stroke, Alzheimer's disease, and peripheral neuropathy. Inhibitors for caspases and related cysteine proteases have potential for the treatment of stroke, Alzheimer's disease, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), spinal muscular atrophy, inflammation, periodontal disease, parasite infection, and cancer. Both mechanism-based (or suicide) and transition-state inhibitors are being developed. Other research is concerned with elucidating the role of serine proteases (granzymes) and dipeptidyl peptidase I, which function in the killing of both virally infected cells and tumor cells by natural killer cells and cytotoxic T-lymphocytes.

Recent Publications

"Peptidyl Allyl Sulfones: A New Class of Inhibitors for Clan CA Cysteine Proteases," Gštz, M. A, Caffrey, C. R., Hansell, E., McKerrow, J. H., and Powers, J. C., Bioorganic & Medicinal Chemistry, 2004, 12, 5203-5211.

"Design and Evaluation of Inhibitors for Dipeptidyl Peptidase I (Cathepsin C)," Kam, C.-M., Gštz, M. G., Koot, G., McGuire, M., Thiele, D., Hudig, D. and Powers. J. C., Arch. Biochem. Biophys., 2004 427, 123-134.

"Evidence that Unrestricted Legumain Activity is Involved in Disturbed Epidermal Cornification in Cystatin M/E Deficient Mice," Zeeuwen, P. L. J. M., van Vlijmen-Willems, I. M. J. J., Olthuis, D., Johansen, H. T., Hitomi, K., Hara-Nishimura, I., Powers, J. C., James, K. E., op den Camp, H. J., Lemmens, R. and Schalkwijk, J., Human Molecular Genetics, 2004, 13, 1069-1079. This paper also included a cover photograph.

"Aza-peptide Michael acceptors: A new class of inhibitors specific for caspases and other clan CD cysteine proteases," O. D. Ekici, M. G. Gštz, K. E. James, Z. Z. Li, B. J. Rukamp, J. L. Asgian, C. R. Caffrey, E. Hansell, J. Dvor‡k, J. H. McKerrow, J. Potempa, J. Travis, J. Mikolajczyk, G. S. Salvesen, J. C. Powers, J. Med. Chem., 2004, 47.

"Design, synthesis, and evaluation of aza-peptide epoxides as selective and potent inhibitors of caspases-1, -3, -6, and -8," K. E. James, J. L. Asgian, Z. Z. Li, O. D. Ekici, J. R. Rubin, J. Mikolajczyk, G. S. Salvesen, J. C. Powers, J. Med. Chem., 2004, 47, 1553-1574.

"Subsite specificities of granzyme M: A study of inhibitors and newly synthesized thiobenzyl ester substrates," B. J. Rukamp, C. -M. Kam, S. Natarajan, B. W. Bolton, M. J. Smyth, J. M. Kelly, J. C. Powers, Arch. Biochem. Biophys., 2004, 421, 9-22.

"Calpain inhibition protects against taxol-induced sensory neuropathy," M. S. Wang, A. A. Davis, D. G. Culver, Q. Wang, J. C. Powers, J. D. Glass, Brain, 2004, 127, 1-9.

"Aza-peptide epoxides: Potent and selective inhibitors of schistosoma mansoni and pig kidney legumains (asparaginyl endopeptidases)," K. E. James, M. G. Gštz, C. R. Caffrey, E. Hansell, W. Carter, A. J. Barrett, J. H. McKerrow, J. C. Powers, Biol. Chem., 2003, 384, 1613-1618.

"Synthesis of C-terminal modified peptides," J. C. Powers in Houben-Weyl Methods of Organic Chemistry. Synthesis of Peptides and Peptidomimetics (M. Goodman, A. Felix, L. Moroder, C. Toniolo, C. eds), Georg Thieme Verlag, Stuttgart and New York, 2003, E 22d, 199-199.

"Peptide aldehydes," J. A. Krauser, J. C. Powers, in Houben-Weyl Methods of Organic Chemistry. Synthesis of Peptides and Peptidomimetics (M. Goodman, A. Felix, L. Moroder, C. Toniolo, Eds), Georg Thieme Verlag, Stuttgart and New York, 2003, E 22d, 199-217.

"Diazomethyl ketone derivatives of peptides," C. -M. Kam, J. C. Powers, in Houben-Weyl Methods of Organic Chemistry. Synthesis of Peptides and Peptidomimetics (M. Goodman, A. Felix, L. Moroder, C. Toniolo, Eds), Georg Thieme Verlag, Stuttgart and New York, 2003, E 22d, 218-220.

"Peptide halomethyl ketones (excluding fluoromethyl ketones)," K. E. Adlington, J. C. Powers, in Houben-Weyl Methods of Organic Chemistry. Synthesis of Peptides and Peptidomimetics (M. Goodman, A. Felix, L. Moroder, C. Toniolo, Eds), Georg Thieme Verlag, Stuttgart and New York, 2003, E 22d, 221-225.

"Peptide fluoromethyl, difluoromethyl, and perfluoroalkyl ketones," K. E. Adlington, J. C. Powers, in Houben-Weyl Methods of Organic Chemistry. Synthesis of Peptides and Peptidomimetics (M. Goodman, A. Felix, L. Moroder, C. Toniolo, Eds), Georg Thieme Verlag, Stuttgart and New York, 2003, E 22d, 226-243.

"Peptide hydroxamic acids," N. Nishino, J. C. Powers, in Houben-Weyl Methods of Organic Chemistry. Synthesis of Peptides and Peptidomimetics (M. Goodman, A. Felix, L. Moroder, C. Toniolo, Eds), Georg Thieme Verlag, Stuttgart and New York, 2003, E 22d, 256-271.

"Peptide phosphonates," J. Oleksyszyn, J. C. Powers, in Houben-Weyl Methods of Organic Chemistry. Synthesis of Peptides and Peptidomimetics (M. Goodman, A. Felix, L. Moroder, C. Toniolo, Eds), Georg Thieme Verlag, Stuttgart and New York, 2003, E 22d, 285-303.

"Peptide thiols," C. -M. Kam, J. C. Powers, in Houben-Weyl Methods of Organic Chemistry. Synthesis of Peptides and Peptidomimetics (M. Goodman, A. Felix, L. Moroder, C. Toniolo, Eds), Georg Thieme Verlag, Stuttgart and New York, 2003, E 22d, 304-315.

"Peptide thioesters," C. -M. Kam, J. C. Powers, in Houben-Weyl Methods of Organic Chemistry. Synthesis of Peptides and Peptidomimetics (M. Goodman, A. Felix, L. Moroder, C. Toniolo, Eds), Georg Thieme Verlag, Stuttgart and New York, 2003, E 22d, 316-321.

"Peptide dithioesters," C. -M. Kam, J. C. Powers, in Houben-Weyl Methods of Organic Chemistry. Synthesis of Peptides and Peptidomimetics (M. Goodman, A. Felix, L. Moroder, C. Toniolo, Eds), Georg Thieme Verlag, Stuttgart and New York, 2003, E 22d, 322-328.

"Peptide vinyl sulfones," C. -M. Kam, J. C. Powers, in Houben-Weyl Methods of Organic Chemistry. Synthesis of Peptides and Peptidomimetics (M. Goodman, A. Felix, L. Moroder, C. Toniolo, Eds), Georg Thieme Verlag, Stuttgart and New York, 2003, E 22d, 329-333.

"Peptide nitriles," C. -M. Kam, J. C. Powers, in Houben-Weyl Methods of Organic Chemistry. Synthesis of Peptides and Peptidomimetics (M. Goodman, A. Felix, L. Moroder, C. Toniolo, Eds), Georg Thieme Verlag, Stuttgart and New York, 2003, E 22d, 334-339.