Synthesis and in vitro Characterization of Triazole-Stapled Bim Alpha-Helical Peptides
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Authors
Kinch, Logan D.
Issue Date
2010
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
The Bcl-2 protein family has been shown to play a vital role in the cell apoptosis process. Within this family is Bim, a pro-apoptotic protein, which forms a heterodimer with Bcl-2 allowing for the eventual release of caspases from the mitochondria leading to cell death, a necessity for normal cell functioning. Optimizing this interaction between the two proteins may allow for the development of tracers for in vitro and in vivo assays and possibly a means to combat the rapid proliferation of cells, a hallmark of cancer. The goal of the research presented in this paper is to stabilize the region of the Bim peptide, residues 85-106, which interacts with Bcl-2. Successful synthesis will induce α-helicity allowing for increased binding affinity and cell permeability as well as inhibition of proteolytic degradation. Stabilization was attempted by means of “click chemistry” and the formation of a triazole staple in an i and i+4 amino acid position. Analysis of the stapled peptides through a fluorescence polarization competitive binding assay showed minimal difference in IC50 values between linear and stapled α-helical peptides.
Description
vii, 22 p.
Citation
Publisher
Kalamazoo College
License
U.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder. All rights reserved.