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STUDIES OF HETEROGENEOUS MACROMOLECULES USING NOVEL ESI MASS SPECTROMETRY BASED APPROACHES

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.
Type
campusfive
article
dissertation
Date
2022-02-01
Publisher
Rights
License
http://creativecommons.org/licenses/by-nc-nd/4.0/