Drug Discovery Without a Lead: Chemical Modulators of the Heat Shock Protein 70 Chaperone Complex

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Authors
Briski, Robert
Issue Date
2011
Type
Thesis
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en_US
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Abstract
Protein misfolding and aggregation is a common theme among a variety of sporadic diseases. While the etiology of sporadic proteopathies (Alzheimer's, Parkinson's, prions, etc) continues to elude medicine, the opportunity to provide patients with therapeutics may reside in perturbing the mechanisms of protein misfolding and aggregation. A class of proteins found in the human body, known as molecular chaperones, have the unique feature of binding and releasing hydrophobic regions of polypeptides. One way the cell has manipulated this feature involves directing molecular chaperones to decrease the distance between hydrophobic regions on a polypeptide relative to hydrophobic regions on an adjacent peptide. The resulting increased probability of intramolecular collisions enables polypeptides to overcome the energy barrier associated with proper protein folding. This may be achieved through the binding and release, translocation, or degradation of polypeptides. To probe the role of chaperones in sporadic proteopathies, this study performed a random screen to identify drug molecules capable of regulating each role of the chaperone heat shock protein 70 (hsp70). Four small molecules were identified as potential regulators of hsp70 chaperone activity. /^K
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vi, 22 p.
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Kalamazoo College
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U.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder. All rights reserved.
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