Jakubek, Ryan
(2019)
Insights into the Structure and Hydrogen Bonding Interactions of Polyglutamine Peptides Using UV Resonance Raman Spectroscopy.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Proteins containing expanded polyglutamine (polyQ) tracts are prone to aggregation and fibrillization. This fibrillization is associated with many different neurodegenerative diseases including Huntington’s disease. The pathology of these diseases is poorly understood. This is in part due to the difficulty of studying the structures and fibrillization mechanism of polyglutamine tracts. In this work, we utilize UV resonance Raman (UVRR) spectroscopy, as well as other techniques, to investigate the structures and hydrogen bonding interactions of solution-state, fibril-state, and insoluble forms of polyQ peptides. For example, we find that solution-state polyglutamine peptides can be prepared in an aggregation-prone β-strand-like conformation or an aggregation-resistant PPII-like conformation. We find that longer polyQ peptides have an increased population of aggregation-prone β-strand-like conformation that may contribute to faster aggregation kinetics and decreased age of onset for disease symptoms. We also developed a method to quantitatively correlate the frequency of the amide I (AmI) Raman band to the hydrogen bonding strength between the glutamine side chain C=O oxygen and a hydrogen bond donor. Using this technique, as well as other techniques, we investigated the oligomerization and hydrogen bonding interactions in the various structures of polyQ peptides to examine their role in polyQ aggregation.
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Details
| Item Type: |
University of Pittsburgh ETD
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| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
| Title | Member | Email Address | Pitt Username | ORCID |
|---|
| Committee Chair | Asher, Sanford | | asher | | | Committee Member | Saxena, Sunil | | sksaxena | | | Committee Member | Garrett-Roe, Sean | | sgr | | | Committee Member | van der Wel, Patrick | | pvdwel | |
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| Date: |
27 September 2019 |
| Date Type: |
Publication |
| Defense Date: |
7 July 2019 |
| Approval Date: |
27 September 2019 |
| Submission Date: |
19 July 2019 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
361 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Dietrich School of Arts and Sciences > Chemistry |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Raman, Polyglutamine |
| Date Deposited: |
27 Sep 2019 15:14 |
| Last Modified: |
27 Sep 2019 15:14 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/37037 |
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