title: Conformation and dynamics of biopharmaceuticals: transition of mass spectrometry-based tools from academe to industry.
abstract: Mass spectrometry plays a very visible role in biopharmaceutical industry, although its use in development, characterization, and quality control of protein drugs is mostly limited to the analysis of covalent structure (amino acid sequence and post-translational modifications). Despite the centrality of protein conformation to biological activity, stability, and safety of biopharmaceutical products, the expanding arsenal of mass spectrometry-based methods that are currently available to probe higher order structure and conformational dynamics of biopolymers did not, until recently, enjoy much attention in the industry. This is beginning to change as a result of recent work demonstrating the utility of these experimental tools for various aspects of biopharmaceutical product development and manufacturing. In this work, we use a paradigmatic protein drug interferon beta-1a as an example to illustrate the utility of mass spectrometry as a powerful tool not only to assess the integrity of higher order structure of a protein drug, but also to predict consequences of its degradation at a variety of levels.
authors: Department of Chemistry, University of Massachusetts-Amherst, Amherst, Massachusetts 01003, USA. Kaltashov@chem.umass.edu
authors: Igor A
authors: IA
authors: Kaltashov
authors: Cedric E
authors: CE
authors: Bobst
authors: Rinat R
authors: RR
authors: Abzalimov
authors: Steven A
authors: SA
authors: Berkowitz
authors: Damian
authors: D
authors: Houde
mesh_terms: D000478:Alkylation; D001688:Biological Products / Q000032:analysis* / Q000737:chemistry*; D004353:Drug Evaluation, Preclinical / Q000379:methods / Q000639:trends; D007221:Industry; D013058:Mass Spectrometry / Q000379:methods* / Q000639:trends*; D011487:Protein Conformation; D011506:Proteins / Q000032:analysis* / Q000737:chemistry*; D018581:Technology Transfer; D014495:Universities
chemical_list: D001688:Biological Products; D011506:Proteins