Engineering cystine-knot peptides for molecular imaging of cancer
Abstract/Contents
- Abstract
- Proteins and peptides are an incredibly versatile class of biological molecules, with a vast array of naturally occurring functions. In cancer, the natural roles of proteins become incorrectly regulated, and the presence of cancer-related proteins on tumor cells can be detected and targeted for diagnosis and treatment. This thesis decribes novel engineered peptides for molecular recognition of cell surface receptors expressed in cancers, and application of these engineered peptides as diagnostic agents to identify solid tumors in mouse models. For this work. three different cystine-knot peptides were used for development and engineering: Agatoxin (AgTx), Agouti-related protein (AgRP), and Ecballium elaterium trypsin inhibitor-II (EETI). In addition, two protein receptors were employed as model tumor targets relevant for molecular imaging of cancer: carbonic anhydrase IX (CA IX) and tumor associated integrin receptors. New methods were developed towards engineering AgTx and AgRP to bind CA IX, and work to produce these peptides for further study and their limitations are described. In a parallel line of research, to further understand the promise of using knottin peptides in cancer imaging, the influence of amino acid loops on tissue biodistribution was examined using engineered AgTx, AgRP, and EETI peptides that bind tumor target integrins in mouse xenograft models. Finally, an engineered EETI knottin peptide that binds tumor-associated integrins was shown to specifically target and illuminate brain tumors in mouse models of medulloblastoma. Importantly, the protein engineering methods and molecular imaging applications described here have promise for influencing the clinical outcome of cancer patients through image-guided surgical resection, disease staging and management, and monitoring the effectiveness of therapeutic treatments.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2012 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Moore, Sarah Jean | |
|---|---|---|
| Associated with | Stanford University, Department of Bioengineering. | |
| Primary advisor | Cochran, Jennifer R | |
| Thesis advisor | Cochran, Jennifer R | |
| Thesis advisor | Contag, Christopher H | |
| Thesis advisor | Graves, Edward (Edward Elliot), 1974- | |
| Thesis advisor | Lin, Michael Z | |
| Advisor | Contag, Christopher H | |
| Advisor | Graves, Edward (Edward Elliot), 1974- | |
| Advisor | Lin, Michael Z |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Sarah Jean Moore. |
|---|---|
| Note | Submitted to the Department of Bioengineering. |
| Thesis | Ph.D. Stanford University 2012 |
| Location | electronic resource |
Access conditions
- Copyright
- © 2012 by Sarah Jean Moore
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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