UBC Theses and Dissertations

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UBC Theses and Dissertations

A potentially stable five-helix bundle cavitein and applications of caviteins in ester hydrolysis and protein-protein interaction Yang, Hui


This thesis will present the study of a peptide sequence that is favourable for forming a five-helix bundle through the use of template assembled synthetic proteins (TASPs), and applications of our synthetic proteins in rate enhancement of ester hydrolysis and protein-protein interactions. Chapter 1 will introduce proteins, de novo protein design, and TASPs. It will also review past and current research on the applications of the synthetic molecules mimicking biological behavior. Chapter 2 will focus on several modified de novo designed peptide sequences that are intended to be more favourable in folding into a five-helix bundle than a four-helix bundle. We found that our designed sequence narrowed the free energy gap between the five-helix bundle and the four-helix bundle relative to the systems where the peptide sequence was designed to favour a four-helix bundle. Chapter 3 will concentrate on investigating the rate enhancement of ester hydrolysis by histidine-containing TASPs. These TASPs increased the rate of ester hydrolysis, and the position of the histidines was found to be relevant to activity. Chapter 4 will detail the attempts at using a template-assembled synthetic protein to inhibit protein-protein interactions between a Bak peptide and a Bcl-xL protein. Our synthesized protein was found to be a good binding partner towards the Bcl-xL protein and manifested moderately enhanced proteolytic resistance. Several heterocaviteins were also synthesized to study both their inhibitive activities to the Bcl-xL protein, and their proteolytic stability. Chapter 5 will summarize and conclude the work throughout this thesis.

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Attribution-NonCommercial-NoDerivs 2.5 Canada