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Dissertation/Thesis Abstract

Disulfide Constrained Peptides: Properties and Applications
by Welch, Jade J., Ph.D., University of Rochester, 2020, 194; 27742923
Abstract (Summary)

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.

Indexing (document details)
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
Subjects: Biochemistry
Keywords: Peptide, Rippled beta-sheets, Self-assembly, siRNA Delivery
Publication Number: 27742923
ISBN: 9798644901326
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