In this Master’s Thesis Research the results can be summarized from two major tasks: (1) In our first task, we utilized our two protein system (BAG-1 and HSP 70) as part of beta testing of a computational software 1 that can take three dimensional x-ray crystallography information about protein complexes and predict the strength of atom –atom interactions between amino-acid residues Open Contact predicts binding hotspots that can be used to identify short amino acid chains or peptides that mimic that particular binding segment of the larger protein. These peptides are called pepidyl-biomimetics. The peptide can potentially act as an antagonist drug by binding to the hotspot on protein A before protein B of the A-B complex can form. Two potential peptide candidates were identified. In particular, a helical peptide was discovered that demonstrated a variety of different types of atom-atom interactions. (2) Our second task is to experimentally test the helical peptide for its ability to block the binding that occurs between the 70-kilodalton Heat Shock Protein (HSP-70) and the Bcl-2 Associated Athanogene (BAG-1) Protein. As reviewed here, the binding between HSP-70 and BAG-1 elicits a cascade of cellular events that maintain high cancer growth rates and a greatly increased resistance to chemotherapy. In addition, BAG-1 has been implicated in a number of onco-signal pathways, as reviewed here, and its inhibition alone is believed to act as an agent against cancer cell growth
| Identifer | oai:union.ndltd.org:vcu.edu/oai:scholarscompass.vcu.edu:etd-3941 |
| Date | 07 December 2012 |
| Creators | Brunn, Jonathan |
| Publisher | VCU Scholars Compass |
| Source Sets | Virginia Commonwealth University |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Theses and Dissertations |
| Rights | © The Author |
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