Identification of Naval Inhibitory Peptides of Protein-Protein Interactions Involved in DNA Repair as Potential Drugs in Breast Cancer Treatment
Annual summary rept. 1 Apr 2002-31 Mar 2003
ILLINOIS UNIV AT CHICAGO
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Protein-protein interactions are critical to almost every cellular process. Disruption of these interactions would effectively interfere with the cells functions and its ability to grow and divide normally. The Rad51 and Rad52 proteins are important proteins involved in DNA repair. Rad51 acts as a hexamer binding single-stranded DNA to drive strand exchange during homologous recombination. By blocking Rad51 from multimerization we can theoretically disrupt homologous recombination, and thus decrease the efficacy of DNA repair. Deficiency in DNA damage repair will sensitize cells to DNA damaging agents and thus such tumors can be effectively treated with a lower dose of chemotherapeutic agentsradiation. Short peptides of a few amino acids 5-10 have been shown to be enough to destabilize protein-protein interactions. Thus a library of random combinatorial peptides of sufficient complexity will in theory have an inhibitory molecule for any protein-protein interaction. This project will attempt to isolate peptides that inhibit Rad 51 from multimerisation to be used as a chmosensitizing agent during chemoradiotherapy. We plan to use a modified yeast two hybrid screen called the reverse two-hybrid system to isolate such peptides.
- Medicine and Medical Research