Mass Spectrometry Methods for Enhanced Characterization of Biological Systems

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dc.contributor.advisorWilson, Derek J.
dc.creatorSzymkowicz, Lisa Rachel
dc.date.accessioned2019-07-02T16:27:31Z
dc.date.available2019-07-02T16:27:31Z
dc.date.copyright2019-04-15
dc.date.issued2019-07-02
dc.date.updated2019-07-02T16:27:31Z
dc.degree.disciplineChemistry
dc.degree.levelMaster's
dc.degree.nameMSc - Master of Science
dc.description.abstractAs the pharmaceutical industry moves towards larger protein-based therapeutics over chemically synthesized small molecules, there are increasing demands for parallel advancement in the technologies used for quality control of these biologically-derived products (biopharmaceuticals). This work describes the implementation of mass spectrometry (MS)-based methods in three areas where MS is well-positioned to fulfill unmet analytical needs. First, time-resolved electrospray ionization hydrogen-deuterium exchange (TRESI-HDX) and ion mobility spectroscopy (IMS)-MS were used to study conformational dynamics in transient Cytochrome c-lipid interactions. MS was also implemented for proteomic characterization of in-process and purified samples from acellular Pertussis vaccines. Further development of a targeted MS method is described for quantitation of two residual protein toxins, adenylase cyclase toxin (ACT) and dermoneucrotic toxin (DNT), and a glycopeptide, tracheal cytotoxin (TCT), from Bordetella pertussis. Collectively, the results highlight advancement in the application of structural and quantitative proteomics for more effective characterization of next generation biopharmaceuticals.
dc.identifier.urihttp://hdl.handle.net/10315/36339
dc.language.isoen
dc.rightsAuthor owns copyright, except where explicitly noted. Please contact the author directly with licensing requests.
dc.subjectPharmaceutical sciences
dc.subject.keywordsBiochemistry
dc.subject.keywordsChemistry
dc.subject.keywordsMass spectrometry
dc.subject.keywordsProtein dynamics
dc.subject.keywordsCytochrome c
dc.subject.keywordsCardiolipin
dc.subject.keywordsPhospholipids
dc.subject.keywordsMembrane
dc.subject.keywordsProtein conformation
dc.subject.keywordsTime-resolved electrospray ionization
dc.subject.keywordsTRESI
dc.subject.keywordsHydrogen deuterium exchange mass spectrometry
dc.subject.keywordsHDX-MS
dc.subject.keywordsTime-resolved hydrogen deuterium exchange
dc.subject.keywordsTRESI-HDX
dc.subject.keywordsHydrogen-deuterium exchange
dc.subject.keywordsHDX
dc.subject.keywordsIon mobility spectrometry
dc.subject.keywordsIMS
dc.subject.keywordsBiopharmaceuticals
dc.subject.keywordsVaccines
dc.subject.keywordsBordetella pertussis
dc.subject.keywordsPertussis
dc.subject.keywordsWhooping cough
dc.subject.keywordsQuantitation
dc.subject.keywordsToxins
dc.subject.keywordsParallel reaction monitoring
dc.subject.keywordsProtein quantitation
dc.subject.keywordsProteomics
dc.subject.keywordsTargeted proteomics
dc.subject.keywordsAdenylase cyclase toxin
dc.subject.keywordsDermoneucrotic toxin
dc.subject.keywordsTrachael cytotoxin
dc.subject.keywordsLiquid chromatography
dc.subject.keywordsLC-MS
dc.subject.keywordsTandem mass spectrometry
dc.subject.keywordsLC-MS/MS
dc.subject.keywordsResidual toxins
dc.titleMass Spectrometry Methods for Enhanced Characterization of Biological Systems
dc.typeElectronic Thesis or Dissertation

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