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Author ORCID Identifier

0000-0002-4178-4409

AccessType

Campus-Only Access for Five (5) Years

Document Type

dissertation

Degree Name

Doctor of Philosophy (PhD)

Degree Program

Chemistry

Year Degree Awarded

2022

Month Degree Awarded

February

First Advisor

Igor A. Kaltashov

Second Advisor

Richard W. Vachet

Third Advisor

Mingxu You

Fourth Advisor

Stephen J. Eyles

Subject Categories

Analytical Chemistry

Abstract

Structural heterogeneity remains one of the most significant factors complicating (and in some extreme cases making impossible) electrospray ionization mass spectrometry (ESI MS)-based analysis in a variety of fields ranging from personalized medicine to industrial-scale production of recombinant proteins, including extensively glycosylated proteins, antibody-drug conjugates, gene therapy products, and heparin-derived medicines. The broad mass distribution leads to a significant overlap of ionic signals representing different charge states, resulting in a continuum spectrum with no distinguishable features that can be used to determine the ionic charge and calculate the mass. To address these problems, novel mass spectrometry-based approaches are developed that incorporate with gas-phase ion/ion reactions to expand the capabilities of ESI MS in the field of structurally heterogeneous macromolecules and their assemblies. The list includes SRAS-CoV-2 spike protein and its complexes with the host cell receptor, immunogenic complexes formed by heparin and platelet factor 4 in the development of viii heparin-induced thrombocytopenia disorder, large complexes formed by antibodies cross-linked by bivalent antigens, and haptoglobin and its complexes with hemoglobin.

DOI

https://doi.org/10.7275/26830739.0

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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