Peptide Aptamers as Modulators of Bax Mediated Apoptosis in Breast Cancer Cells
Final rept., 1 May 2003-31 Oct 2004
MCMASTER UNIV HAMILTON (ONTARIO)
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In many breast cancer cells, expression of the programmed cell death apoptosis promoting protein Bax is higher than in normal cells, yet surprisingly the cells do not die. This observation suggests that one of the ways that breast cancers avoid undergoing apoptosis that would normally clear the tumor from the body at an early stage is by preventing Bax activation. Thus, we hypothesized that agents that specifically but inefficiently activate Bax would selectively eradicate breast cancer cells. To test the hypothesis that activation of Bax would selectively induce apoptosis in breast cancer cells requires an agent that will act directly upon the Bax protein to activate it. To provide a reagent that would demonstrate proof-of-principle as well as provide a lead compound for drug discovery programs, aptamers small peptides or nucleic acids with high affinity and selectivity were selected for different conformers of Bax by Covalent Display and SELEX. Covalent Display libraries of aptamers lacked sufficient diversity for the selection of high affinity aptamers. This was due to inefficient binding of P2A to DNA. Two other approaches to selecting aptamers were implemented and yielded promising preliminary results.
- Medicine and Medical Research
- Anatomy and Physiology