Getting to the core of protein pharmaceuticals--Comprehensive structure analysis by mass spectrometry

European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V
Ulrike LeursKasper D Rand

Abstract

Protein pharmaceuticals are the fastest growing class of novel therapeutic agents, and have been a major research and development focus in the (bio)pharmaceutical industry. Due to their large size and structural diversity, biopharmaceuticals represent a formidable challenge regarding analysis and characterization compared to traditional small molecule drugs. Any changes to the primary, secondary, tertiary or quaternary structure of a protein can potentially impact its function, efficacy and safety. The analysis and characterization of (structural) protein heterogeneity is therefore of utmost importance. Mass spectrometry has evolved as a powerful tool for the characterization of both primary and higher order structures of protein pharmaceuticals. Furthermore, the chemical and physical stability of protein drugs, as well as their pharmacokinetics are nowadays routinely determined by mass spectrometry. Here we review current techniques in primary, secondary and tertiary structure analysis of proteins by mass spectrometry. An overview of established top-down and bottom-up protein analyses will be given, and in particular the use of advanced technologies such as hydrogen/deuterium exchange mass spectrometry (HDX-MS) for higher-orde...Continue Reading

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Citations

Dec 31, 2015·Expert Review of Proteomics·Danilo DonnarummaNathalie Norais
Jun 22, 2016·Journal of Pharmaceutical and Biomedical Analysis·Maria Kristina ParrHouda Montacir
Sep 1, 2016·Journal of Pharmaceutical Sciences·Zeinab E NazariKasper D Rand
Feb 15, 2017·Journal of the American Society for Mass Spectrometry·Damian J HoudeSteven A Berkowitz
Oct 29, 2020·Analytical Chemistry·John R EngenThomas E Wales

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