A protein surface properties perspective on multimodal chromatography : from fundamental understanding to predictive tools
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Authors
Robinson, Julie Renee
Issue Date
2018-12
Type
Electronic thesis
Thesis
Thesis
Language
ENG
Keywords
Chemical engineering
Alternative Title
Abstract
During downstream process development of proteins, high throughput screening is conduct- ed to identify conditions for multimodal steps due to the difficulty of identifying important binding regions and predicting selectivity a priori. This work addressed these challenges by connecting protein surface properties to protein behavior in multimodal systems to increase understanding of ligand-protein interactions. This knowledge informed the creation of predictive models to facilitate in silico process development of multimodal steps. A library of multimodal anion exchange (MM AEX) prototypes was designed to investigate the impact of aromatic ring substituents on selectivity for a diverse set of model proteins. Aliphatic prototypes showed dramatic changes in selectivity with important implications for mAb monomer-aggregate separa- tions. A quantitative structure activity relationship (QSAR) model was developed to predict protein retention in the various MM AEX resins.
Description
December 2018
School of Engineering
School of Engineering
Full Citation
Publisher
Rensselaer Polytechnic Institute, Troy, NY