The first part of this thesis (Chapter 2) describes a kinetic analysis comparing peptide assembly into pleated versus rippled β-sheets. The first experimental example of rippled β-sheets was reported in 2011 despite predictions by Pauling and Corey in 1953. Rippled β-sheets are a two-component structure formed by coassembly of an equimolar mixture of enantiomeric peptides, resulting in arrangement of alternating L/D strands within the β-sheet. There is still much that is not understood about rippled β-sheets in comparison to the properties and structure of pleated β-sheets. Previous studies have found a thermodynamic advantage for forming rippled β-sheets, but without structural information or an idea of the energetic landscape, it is unclear why this is the case. The purpose of the work described in Chapter 2 is to find if there is a kinetic preference for rippled β-sheets over pleated β-sheets.
The second part of this thesis (Capters 3 and 4) describes the application of these peptides as a novel cell-penetrating peptide delivery vector. The work in Chapter 3 details initial design and proof-of-concept of disulfide constrained cyclic amphipathic peptides (dcCAPs) for delivery of siRNA both in vitro and in vivo. dcCAPs are able to condense with siRNA to form nanoparticles. Chapter 4 contains efforts to elucidate the mechanism of cellular internalization and gain an understanding of the structural basis for dcCAP-siRNA binding. Understanding interactions between dcCAP and siRNA during nanoparticle formation as well as interactions between the dcCAP-siRNA nanoparticle and the cell membrane will allow us to design an idealized siRNA carrier.
|Advisor:||Nilsson, Bradley L.|
|Commitee:||Frontier, Alison, Bren, Kara, Dean, David A., Benoit, Danielle|
|School:||University of Rochester|
|Department:||School of Arts and Sciences|
|School Location:||United States -- New York|
|Source:||DAI-B 81/11(E), Dissertation Abstracts International|
|Keywords:||Peptide, Rippled beta-sheets, Self-assembly, siRNA Delivery|
Copyright in each Dissertation and Thesis is retained by the author. All Rights Reserved
The supplemental file or files you are about to download were provided to ProQuest by the author as part of a
dissertation or thesis. The supplemental files are provided "AS IS" without warranty. ProQuest is not responsible for the
content, format or impact on the supplemental file(s) on our system. in some cases, the file type may be unknown or
may be a .exe file. We recommend caution as you open such files.
Copyright of the original materials contained in the supplemental file is retained by the author and your access to the
supplemental files is subject to the ProQuest Terms and Conditions of use.
Depending on the size of the file(s) you are downloading, the system may take some time to download them. Please be