Diseases; Chemicals and Drugs; Health Care
The Schepartz laboratory applies the tools of chemistry, cell biology, biochemistry, and molecular imaging to study and manipulate protein networks and assemblies inside the cell. Our approach centers on the design and synthesis of molecules–miniature proteins, ß-peptides, fluorolipids, and designer fluorophores–that, by virtue of their structure or function, probe the functional roles of protein interactions or networks in the native cellular or organismal environment. Current topics include the design of miniature protein catalysts that rewire cellular circuits, the application of cell-permeable designer fluorophores to characterize transmembrane information transfer, the synthesis and application of orthogonal cellular compartments, and the design of protein-like assemblies of ß-peptides that possess catalytic function. For more information, please visit our group web site http://www.schepartzlab.yale.edu/.
Extensive Research Description
Our research group is large and we investigate a broad range of scientific questions at the combined interface of chemistry, biology, and medicine. A subset of these projects is listed below.
1. Design and application of a cell signaling node to reactivate p53.
2. Genomic, high contact analysis of peptidomimetic release from early endosomes.
3. Illuminating cconformational changes controlling ligand-specific activation of EGFR family members.
4. Design and synthesis of a beta-peptide catalyst for the synthesis and cleavage of glycosidic bonds.
5. Design of b-peptide agonists of class B GPCRs.
6. Design and application of fluorolipid-based orthogonal cellular compartments.
- Visualizing tyrosine kinase activity with bipartite tetracysteine display. S. Ray-Saha & A. Schepartz, ChemBioChem. 2010, 11, 2089-2091
- Direct visualization of protein association in living cells with complex-edited electron microscopy. R.J. Dexter & A. Schepartz, Angew. Chem. 2010, 49, 7952-7954.
- Selective recognition of protein tetraserine motifs with a cell-permeable, pro-fluorescent bis-boronic acid. T.L. Halo, J. Appelbaum, E.M. Hobert, D.M. Balkin, & A. Schepartz, J. Am. Chem. Soc. 2009, 131, 438-439
- Toward ß-amino acid proteins: design, synthesis, and characterization of a fifteen kilodalton ß-peptide tetramer. E.J. Petersson & A. Schepartz, J. Am. Chem. Soc. 2008, 130, 821-823
- Intrinsically cell-permeable miniature proteins based on a minimal cationic PPll motif. D.S. Daniels & A. Schepartz, J. Am. Chem. Soc. 2007, 129, 14578-14579
- Luedtke, N.W., Dexter, R.J., Fried, D.B., and Schepartz, A. (2007). Surveying polypeptide and protein domain conformation and association with FIAsH and ReAsH. Nat. Chem. Biol. 3: 779-78