Charge Pairs and Mutations in Collagen Mimetic Peptides

Date
2017-04-10
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Abstract

This thesis will present insights into natural type I collagen based upon studies with collagen mimetic peptides. Natural collagen is a fibrous protein with challenging properties, such as solubility, which makes it difficult to study through analytical methods such as nuclear magnetic resonance spectroscopy. Collagen mimetic peptides are a flexible and controlled model system that imitates natural type I collagen structure, a triple helix, on a smaller scale, from over 1000 amino acids to around 30 amino acids. Chapter one will explore the development of collagen mimetic peptides and review the current design principle to form composition and register specific triple helices. Chapter two will illustrate the power of charge pairing in the triple helix with the creation of a triple helix with an extended offset through axial charge pairing. This is the first triple helix with an extended offset, proving that the offset triple helix is possible, even when it is not incorporated into a fiber. Chapters three and four will model mutations from Osteogenesis Imperfecta, a type I collagen disease, in collagen mimetic peptides. Osteogenesis Imperfecta results from mutations of the requisite glycines in the Xaa-Yaa-Gly repeat of collagen. Mutations in both the A and B chains of an AAB triple helix will be created, and their impact on the composition, stability, and structure of the triple helix will be examined through circular dichroism and nuclear magnetic resonance experiments. The results of those experiments will be used to create molecular models of the mutated triple helices. This series of studies gives insight into the forces in the triple helix: the destabilizing force of a mutation, the stabilizing force of hydrogen bonds, and the stabilizing, yet constricting, force of axial charge pairs. In these model systems, the mutation was able to direct the composition and register of the triple helix, where the triple helix with the lowest number of mutations would fold, even if it is not the most stabilized via charge pairing.

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Degree
Doctor of Philosophy
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Thesis
Keywords
collagen
Citation

Clements, Katherine Ann. "Charge Pairs and Mutations in Collagen Mimetic Peptides." (2017) Diss., Rice University. https://hdl.handle.net/1911/96065.

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