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Insights into the Structure and Hydrogen Bonding Interactions of Polyglutamine Peptides Using UV Resonance Raman Spectroscopy

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 (Unpublished)

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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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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Jakubek, Ryanrsj2@pitt.edursj2
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairAsher, Sanfordasher
Committee MemberSaxena, Sunilsksaxena
Committee MemberGarrett-Roe, Seansgr
Committee Membervan der Wel, Patrickpvdwel
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


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