Mass Spectrometry-Based Analysis to Investigate the Physiochemical and Proteomic Properties of Viral Sensitizers
Public Deposited- Resource Type
- Creator
- Abstract
Attenuated viruses hold great potential in viral-based therapies including vaccine production and oncolytic virotherapy. Both applications are hindered by poor intercellular infection propagation due to genetic heterogeneity amongst target cells in regard to antiviral response functionality. Our collaborative research group has developed a novel solution to address this problem: first-in-class small molecules termed viral sensitizers (VSes) that potentiate attenuated viral infection in resistant cells. Liquid chromatography mass spectrometry (LC-MS) methods using various scanning modes were developed to characterize the poor physiochemical properties of the first lead compound. Furthermore, LC-MS methods were applied in a VSe library screen and quality assurance experiments. New lead compounds were identified with improved plasma stability and retained activity. Pharmacokinetic and metabolomic studies using lead VSes revealed that glutathione stability and tumour penetrance are important considerations for future experiments. MS-based and gel-based proteomic experiments used target identification techniques to elucidate the VSe mechanism of action.
- Subject
- Language
- Publisher
- Thesis Degree Level
- Thesis Degree Name
- Thesis Degree Discipline
- Identifier
- Rights Notes
Copyright © 2015 the author(s). Theses may be used for non-commercial research, educational, or related academic purposes only. Such uses include personal study, research, scholarship, and teaching. Theses may only be shared by linking to Carleton University Institutional Repository and no part may be used without proper attribution to the author. No part may be used for commercial purposes directly or indirectly via a for-profit platform; no adaptation or derivative works are permitted without consent from the copyright owner.
- Date Created
- 2015
Relations
- In Collection:
Items
Thumbnail | Title | Date Uploaded | Visibility | Actions |
---|---|---|---|---|
macklin-massspectrometrybasedanalysistoinvestigate.pdf | 2023-05-05 | Public | Download |