Instrumental Analysis of Pasylated Asparaginase, JZP-341, A Pre-Clinical Drug Candidate

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dc.contributor.advisorKrylov, Sergey N.
dc.contributor.authorGhaffari, Shakiba
dc.date.accessioned2023-12-08T14:48:40Z
dc.date.available2023-12-08T14:48:40Z
dc.date.issued2023-12-08
dc.date.updated2023-12-08T14:48:39Z
dc.degree.disciplineChemistry
dc.degree.levelMaster's
dc.degree.nameMSc - Master of Science
dc.description.abstractBio-betters are second-generation biopharmaceutical drugs that aim to improve the original drug’s pharmacokinetic or pharmacodynamic properties through minor physical modifications. Bio-betters require extensive characterization. Here, we investigate: JZP-341, a long-acting asparaginase bio-better used to treat leukemia. JZP-341 has a disordered proline-alanine-serine (PAS) tail that increases the drug’s size and thereby its serum half-life. A long serum half-life decreases the dosage frequency, providing more freedom to the patient. We assess the structural heterogeneity, charge heterogeneity, and enzyme kinetics of JZP-341 to better understand the effects of the PAS tail on the drug via the methods of capillary electrophoresis (CE), mass spectrometry (MS), and chromatography. We observe size heterogeneity and charge heterogeneity. We also developed a native capillary gel electrophoresis assay and an automated label-free CE-MS enzyme activity assay to study JZP-341. A detailed understanding of the role of PAS tail on JZP-341 requires further assay development and sophisticated equipment.
dc.identifier.urihttps://hdl.handle.net/10315/41775
dc.languageen
dc.rightsAuthor owns copyright, except where explicitly noted. Please contact the author directly with licensing requests.
dc.subjectAnalytical chemistry
dc.subjectChemistry
dc.subjectBiochemistry
dc.subject.keywordsAsparaginase
dc.subject.keywordsCapillary electrophoresis
dc.subject.keywordsMass spectrometry
dc.subject.keywordsPASylation
dc.titleInstrumental Analysis of Pasylated Asparaginase, JZP-341, A Pre-Clinical Drug Candidate
dc.typeElectronic Thesis or Dissertation

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