Xiong, Kan
(2012)
UV RESONANCE RAMAN STUDIES OF PEPTIDE FOLDING, PEPTIDE FIBRILLIZATION AND Cl- → H2O CHARGE TRANSFER TRANSITION.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Protein folding problem is one of the most important unsolved problems in biology. Many diseases such as Alzheimer disease and Parkinson disease are caused by protein unfolding, protein misfolding and protein aggregation. Understanding molecular mechanism(s) of these diseases could facilitate drug design to treat diseases.
UV resonance Raman spectroscopy (UVRR) is the most useful dilute solution method to quickly determine protein and peptide secondary structure. UVRR enables monitoring of the protein and peptide conformational distributions and Gibbs free energy landscapes along the Ramachandran Ψ coordinate.
We utilized UVRR to examine the dependence of Gibbs free energy landscapes of an α-helical peptide on solution environment such as salt species (Chapter 3) and alcohol species (Chapter 4). We also examined poly-L-glutamate (PGA) conformation dependence on salt concentrations, and surprisingly found that high concentrations of NaCl and KCl do not alter the unfolded PPII and 2.51-helix conformations of PGA (Chapter 5).
In Chapter 6, we reported the first time experimental measurements of Ramachandran Ψ-angle distributions for intrinsically disordered peptides: the N-terminal peptide fragment (Residues 17-29) of tumor suppressor p53 and its P27S mutant form. We also measured UVRR spectra of Leu26 deuterated peptides to determine conformational distributions of Leu26 in the p53 peptides.
In Chapter 7, we reported the first experimental measurements of the impact of ion binding on poly-L-lysine (PLL) (un)folding kinetics. We also examined PLL (un)folding coordinate(s) to obtain insight into PLL (un)folding mechanism(s).
In Chapter 8, we developed a method and for the first time directly monitored the backbone and side chain hydrogen bonding of a polyGLN peptide whose solution structure can be controlled to either fibrillize or not fibrillize.
In Chapter 9, we utilized UVRR to probe the lowest energy allowed electronic transitions of aqueous solutions containing Cl- salts. We showed that the waters hydrating the Cl- are involved in charge transfer transitions that transfer electron density from Cl- to the water molecules. These charge transfer transitions cause significant change in the H-O-H bond angle in the excited states, which results in a strong enhancement of the preresonance Raman intensity of the water bending modes.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
5 July 2012 |
| Date Type: |
Publication |
| Defense Date: |
13 February 2012 |
| Approval Date: |
5 July 2012 |
| Submission Date: |
8 February 2012 |
| Access Restriction: |
2 year -- Restrict access to University of Pittsburgh for a period of 2 years. |
| Number of Pages: |
239 |
| 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: |
UV resonance Raman spectroscopy, peptide folding, peptide fibrillization, Cl- → H2O charge transfer transition |
| Date Deposited: |
05 Jul 2012 18:46 |
| Last Modified: |
15 Nov 2016 13:56 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/10969 |
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