ORGN 697 |
| Blake R. Peterson, Department of Chemistry, Department of Chemistry, The Pennsylvania State University, 152 Davey Lab, University Park, PA 16802 |
| Small molecules that dimerize proteins in living cells provide powerful probes of biological processes. This approach can identify protein targets of biologically active compounds. We employed X-ray crystal structures of ligand-bound estrogen receptor (ER) proteins to design 7-alpha-substituted derivatives of beta-estradiol that allow the natural product biotin to be displayed on the protein surface. A chimeric estradiol derivative linked to biotin was synthesized that potently heterodimerizes ER and streptavidin proteins in a yeast three hybrid system. This chimera activates reporter gene expression controlled by this protein heterodimerization by as much as 450-fold at 10 micromolar ligand. These results indicate that ERs can serve as efficient platforms for the display of biologically active small molecules to target proteins expressed in the nucleus of yeast cells. This strategy may facilitate the identification of protein targets by screening libraries of proteins in yeast three hybrid systems. |
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Proteins, Peptides, Amino Acids, and Nucleotides
8:30 AM-11:30 AM, Thursday, September 11, 2003 Sheraton New York -- Royal Ballroom B, Oral
Division of Organic Chemistry |