Marbella, Lauren E.
(2012)
INVESTIGATING MITOCHONDRIA PENETRATING PEPTIDES WITH SOLID STATE NMR USING MODEL MEMBRANES.
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
Penetrating peptides are unique peptides that can translocate across membranes in a non-lytic fashion. A new class of penetrating peptides that can target the mitochondria with high specificity have been developed. Targeting the mitochondria is therapeutically valuable, given the organelle’s role in energy production and apoptosis. The peptide we studied is sufficiently cationic and hydrophobic and is hypothesized to reach the mitochondrial matrix. However, the mechanism of translocation remains unknown. In our work, we use solid state NMR to gain insight into the mechanism of translocation of this mitochondria-penetrating peptide. We use static 31P NMR the membrane morphology and peptide-induced structure changes. The paramagnetic relaxation effect examined through 13C MAS NMR was used for insertion depth determination and to distinguish bilayer sidedness. We found that the peptide does not disrupt the lamellarity. Also, at low peptide concentrations the peptide binds to the outer leaflet and at high concentrations crosses the hydrophobic bilayer core and is distributed in both leaflets. Our findings support the electroporation model of translocation, but we did not observe complete translocation of the peptide. We examine the energy associated with crossing the inner mitochondrial membrane to determine the feasibility of the peptide reaching the mitochondrial matrix.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
| Creators | Email | Pitt Username | ORCID  |
|---|
| Marbella, Lauren E. | lem64@pitt.edu | LEM64 | |
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| ETD Committee: |
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| Date: |
1 June 2012 |
| Date Type: |
Publication |
| Defense Date: |
9 June 2011 |
| Approval Date: |
1 June 2012 |
| Submission Date: |
8 February 2012 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
59 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Dietrich School of Arts and Sciences > Chemistry |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
penetrating peptides, mitochondria, NMR spectroscopy, translocation mechanism, lipid-peptide interaction |
| Date Deposited: |
01 Jun 2012 18:30 |
| Last Modified: |
15 Nov 2016 13:55 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/10968 |
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