Cabalteja, Chino
(2020)
Structural and Functional Mimicry of Disulfide-Rich Peptides.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Disulfide-rich peptides have promising applications as bioactive agents, but their utility is attenuated by synthetic challenges and various pharmacological drawbacks including low proteolytic stability. Some of these limitations may be addressed by foldamers – sequence specific oligomers with a propensity to fold into discrete conformations. One established approach to the design of foldamer mimics of peptides with complex folds involves incorporation of unnatural building blocks at strategic sites within the natural sequence. Applied judiciously, these modifications can result in peptide variants with a heterogeneous backbone which can adopt complex native-like folds. These proteomimetics can also display augmented pharmacological properties including improved proteolytic resistance. This study demonstrates the application of this heterogeneous backbone substitution strategy to disulfide-rich peptides in the context of structural mimicry of a computationally designed miniprotein and explores the consequences of peptide backbone modification on the function of a bioactive peptide toxin. Lastly, this work delves into the experimental characterization of a series of model tripeptides for validation of a newly developed force field that can simulate artificial protein-like backbones.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
|
| Date: |
16 September 2020 |
| Defense Date: |
10 September 2020 |
| Approval Date: |
20 January 2021 |
| Submission Date: |
17 September 2020 |
| Access Restriction: |
1 year -- Restrict access to University of Pittsburgh for a period of 1 year. |
| Number of Pages: |
147 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Dietrich School of Arts and Sciences > Molecular Biophysics and Structural Biology |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
peptide synthesis,peptide mimics,non-canonical amino acids |
| Date Deposited: |
20 Jan 2021 18:19 |
| Last Modified: |
20 Jan 2022 06:15 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/39749 |
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