Effective therapeutics are urgently needed to improve the treatment and survival of cancer patients and we believe that targeting the MYC oncogene would fill this gap. Our strategy to achieve this goal involves the design of minimalist hybrid protein inhibitors (MHP) - 25-75 amino acid proteins composed of subdomains of known transcription factor families to generate hybrids that act as structural competitive inhibitors of the Myc/Max:DNA E-box interaction. We have established cell systems, reagents and assays using our prototype MHP, ME47 to evaluate the biological effectiveness of this putative inhibitor as well as subsequently designed MHPs using cell-based proliferation and transformation assays. Omomyc was included as a proof-of-concept control to optimize our systems and gauge the performance of ME47. This research demonstrates for the first time that ME47 exerts desirable biological effects in human cells lines and provides support for the validity of our MHP strategy thus warranting further investigation.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/35641 |
| Date | 15 July 2013 |
| Creators | Lustig, Lindsay |
| Contributors | Penn, Linda Z. |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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