Identification of Novel Inhibitory Peptides of Protein-Protein Interactions Involved in DNA Repair as Potential Drugs in Breast Cancer Treatment
Annual summary 1 Apr 2003-31 Mar 2004
ILLINOIS UNIV AT CHICAGO
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The focus of this grant was to evaluate the DNA repair pathway as a new target for therapeutic intervention and to identify inhibitors of the two pathways of double stranded break repair - Homologous Recombination and Non Homologous End Joining. Most therapeutic agents for breast cancer function by causing DNA damage, either directly ionizing radiation or indirectly topoisomerase inhibitors. The problem with these agents is the generalized toxicity of the treatment. Therefore any agent that can specifically target the breast tumor can be used to sensitize the tumor alone to the DNA damaging agent. We used virtual ligand screening using the DOCK software and 3D structure databases from Available Chemicals directory and National Cancer Institute to identify potential disruptors of the Ku 7O8O DNA binding activity. The top scoring hits from this screen were then tested for biochemical activity using an assay developed inhouse. We have identified and validated 4 novel inhibitors of the Ku complex activity. We plan to test these inhibitors as sensitizing agents to topoisomerase inhibitors in the coming months.
- Medicine and Medical Research