Investigating the Structural Dynamics of Therapeutic Proteins using Time resolved Hydrogen deuterium Exchange Mass Spectrometry
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Abstract
Biopharmaceutical products have drastically grown as essential treatments in clinical settings. Hence, the drug industry is moving towards protein-based therapeutics with increasing demands for parallel advancement in bioanalytical technologies.
This thesis centers around displaying the versatility of coupling front-end analytical methods to mass spectrometers. We implement time-resolved electrospray ionization hydrogen-deuterium exchange (TRESI-HDX) and ion mobility spectroscopy (IMS) MS for uncovering new and exciting insights into therapeutic protein dynamics and protein-substrate interactions on millisecond timescale. Using automated continuous flow injection (CFI) has enhanced the analytical throughput of our results.
Collectively, the implications for these results widen the fundamental understanding of the studied proteins. Understanding the crosstalk between dynamics and function may help scientists to design new and improved therapeutics.