- Department of Chemistry
Pearson Chemical Laboratory
- BE, Chemical Engineering, The Cooper Union, New York, NY, 2000
- PhD, Biophysical Chemistry, Yale University, 2005
- NIH-NRSA Postdoctoral Fellow, Whitehead Institute for Biomedical Research, 2005-09
Bioorganic, Biophysical, & Chemical Biology.
Peptides and their mimetics can target protein surfaces in ways small molecules rarely do, making peptide libraries attractive for screening for nontraditional modes of action. The Kritzer research group takes advantage of peptide and peptidomimetic libraries to bypass many of the disadvantages of small molecule screening. They also explore how modifications such as substitution of peptide bonds with isosteres, amide N-methylation, and head-to-tail cyclization affect the activities, specificities, and bioavailabilities of functional peptides. By combining powerful techniques from organic synthesis, biophysical chemistry, molecular biology and genetics, they are developing new molecules and new strategies to attack cancer, inflammation, and autoimmune diseases.
Selected Publications and Presentations
Analysis of Loops that Mediate Protein-Protein Interactions and Translation into Sub-Micromolar Inhibitors. T. R. Siegert, M. J. Bird, K. M. Makwana and J. A. Kritzer. Journal of the American Chemical Society, 2016, 138 (39), 12876-12884.
Conformational Restriction of Peptides Using Dithiol Bis-Alkylation. L. Peraro, T. R. Siegert, and J. A. Kritzer. Methods in Enzymology,2016, 580, 303-332.
Designing Convergent Chemistry Curricula. L. K. Charkoudian, N. S. Sampson, K. Kumar, and J. A. Kritzer. Nature Chemical Biology,2016, 12, 382-386.
A Bicyclic Peptide Scaffold Promotes Phosphotyrosine Mimicry and Cellular Uptake. J. S. Quartararo, M. R. Eshelman, L. Peraro, H. Yu, J. D. Baleja, Y.-S. Lin, and J. A. Kritzer. Bioorganic and Medicinal Chemistry,2014, 22, 6387-6391.
Solution structure of a designed cyclic peptide ligand for nickel and copper ions M. R. Eshelman, A. R. Aldous, K. P. Neupane, and J. A. Kritzer. Tetrahedron, 2014, 70, 7651-7654.
Part of a special issue on Peptide Macrocycles.
Comprehensive Analysis of Loops at Protein-Protein Interfaces for Macrocycle Design. J. Gavenonis*, B. S. Sheneman*, T. R. Siegert*, M. R. Eshelman, and J. A. Kritzer. Nature Chemical Biology, 2014, 10, 716-722.
*these authors contributed equally to this work
Structured Cyclic Peptides that Bind the EH Domain of EHD1. A. Kamens, R. J. Eisert, T. Corlin, J. D. Baleja, and J. A. Kritzer. Biochemistry, 2014,53, 4758-4760.
Potential C-terminal-domain Inhibitors of Heat Shock Protein 90 Derived from a C-terminal Peptide Helix. J. Gavenonis, N. E. Jonas, and J. A. Kritzer.Bioorganic and Medicinal Chemistry, 2014, 22, 3989-3993.
Metal-Binding and Redox Properties of Substituted Linear and Cyclic ATCUN Motifs.K. P. Neupane, A. R. Aldous, and J. A. Kritzer. Journal of Inorganic Biochemistry, 2014, 139, 65-76.
Versatile Substrates and Probes for IgA1 Protease Activity S. K. Choudary, J. Qiu, A. G. Plaut, J. A. Kritzer. ChemBioChem., 2013,14, 2007-2012.
Macrocyclization of the ATCUN Motif Controls Metal Binding and Catalysis, K. P. Neupane, A. R. Aldous, and J. A. Kritzer. Inorg. Chem. 2013, 52, 2729-2735.
Getting in Shape: Controlling Peptide Bioactivity and Bioavailability Using Conformational Constraints, J. E. Bock, J. Gavenonis, and J. A. Kritzer. ACS Chem. Biol. 2013, 8, 488-499.
"Peptide Bicycles that Inhibit the Grb2 SH2 Domain". J. S. Quartararo, P. Wu and J. A. Kritzer, ChemBioChem, 2012, 6, 868-870.
"Compounds from an unbiased chemical screen reverse both ER-to-Golgi trafficking defects and mitochondrial dysfunction in Parkinson disease models", L. J. Su, P. K. Auluck, T. F. Outeiro, E. Yeger-Lotem, J. A. Kritzer, D. F. Tardiff, K. E. Strathearn, F. Liu, S. Cao, S. Hamamichi, K. J. Hill, K. A. Caldwell, G. W. Bell, E. Fraenkel, A. A. Cooper, G. A. Caldwell, J. M. McCaffery, J. C. Rochet, and S. Lindquist. Dis. Model. Mech., 2010, 3, 194-208.
"Beyond discovery: Probes that grab, see and poke", J. A. Kritzer, Nat. Chem. Biol., 2010, 6, 868-870. (Perspective)
"Stapled peptides: Magic bullets in nature's arsenal", J. A. Kritzer, Nat. Chem. Biol., 2010, 6, 566-567. (News and Views)
"Rapid selection of cyclic peptides that reduce alpha-synuclein toxicity in yeast and animal models", J. A. Kritzer, S. Hamamich2, J. M. McCaffery, S. Santagata, T. A. Naumann, K. A. Caldwell, G. A. Caldwell, and S. Lindquist, Nat. Chem. Biol., 2009, 5, 655-663.
"Encodable Activators of Src Family Kinases", C. D. Zellefrow, J. S. Griffiths, S. Saha, A. M. Hodges, J. L. Goodman, J. Paulk, J. A. Kritzer, A. J. Schepartz, J. Am. Chem. Soc. 2006, 128, 16506–07.
"Miniature protein inhibitors of the p53-hDM2 interaction", J. A. Kritzer, R. Zutshi, M. Cheah, F. Ann Ran, R. Webman, T. M. Wongjirad, and A. Schepartz, ChemBioChem, 2006, 7, 29-31.
"A Rapid Library Screen for Tailoring β-Peptide Structure and Function", J. A. Kritzer, N. W. Luedtke, E. A. Harker, and A. Schepartz, J. Am. Chem. Soc., 2005, 127, 14584–14585.
"Solution Structure of a β-Peptide Ligand for hDM2", J. A. Kritzer, M. E. Hodsdon, and A. Schepartz, J. Am. Chem. Soc., 2005, 127, 4118–4119.