Peptide Aptamers as Modulators of Bax Mediated Apoptosis in Breast Cancer Cells
Abstract
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2004
- Accession Number
- ADA433947
Entities
People
- David William Andrews
Organizations
- McMaster University