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Nuclear Magnetic Resonance Spectroscopy applications for Bioindustry and Bioprocessing

Tucker, Robyn Grace (2015) Nuclear Magnetic Resonance Spectroscopy applications for Bioindustry and Bioprocessing. Master of Science by Research (MScRes) thesis, University of Kent. (doi:10.22024/UniKent/01.02.50783) (Access to this publication is currently restricted. You may be able to access a copy if URLs are provided) (KAR id:50783)

Language: English

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[thumbnail of 221Robyn Tucker Final Thesis Oct 2015.pdf]
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The presence of aggregates in protein-based pharmaceuticals clearly needs to be addressed and monitored. A single analytical method that accurately identifies and measures the levels of these protein variants does not yet exist. However, this project has successfully demonstrated the concept that Nuclear Magnetic Resonance (NMR) spectroscopy can be used to detect early stage soluble aggregates as well as monitor subtle changes in proteins that are the result of formulation. The self-aggregation of biopharmaceuticals can alter many properties of a drug that result in a decrease of efficacy, altered pharmacokinetics, reduced stability and reduced shelf life. These problems raise a number of concerns about the safety and success of any drug. In recent years, aggregation has become a central concern and is thought to be behind many formulation problems encountered in the pharmaceutical industry today. This study examined the stability of Glucose Oxidase and Immunoglobulin G under different stress conditions that create soluble aggregates. Aggregates were confirmed using polyacrylamide gel and chromatographic methods followed with analysis using saturation transfer difference (STD) NMR. Different probe molecules were investigated with paracetamol and 8-anilinonaphthalene-1-sulfonic acid (ANS) identified as most optimal from the subset studied. STD NMR was shown to qualitatively detect soluble aggregates with preliminary data supporting the approach as quantitative as data suggests signal intensity is proportional to aggregate concentration. Also, NMR approaches were investigated to monitor protein folding, structure and aggregation in the presence of glucose as a model formulation excipient. Preliminary results monitoring structural differentiation between stressed samples of Immunoglobulin G and Lysozyme demonstrated NMR could detect subtle changes in the proteins after they were incubated in a glucose matrix. These combined results demonstrate the potential of NMR spectroscopy in biopharmaceutical quality control.

Item Type: Thesis (Master of Science by Research (MScRes))
Thesis advisor: Howard, Mark
DOI/Identification number: 10.22024/UniKent/01.02.50783
Additional information: The author of this thesis has requested that it be held under closed access. We are sorry but we will not be able to give you access or pass on any requests for access 04/03/2022
Uncontrolled keywords: Nuclear Magnetic Resonance Spectroscopy applications for Bioindustry and Bioprocessing
Subjects: Q Science > QD Chemistry
Divisions: Divisions > Division of Natural Sciences > Biosciences
Depositing User: Users 1 not found.
Date Deposited: 06 Oct 2015 13:00 UTC
Last Modified: 04 Mar 2022 14:16 UTC
Resource URI: (The current URI for this page, for reference purposes)
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