Department of Chemistry, University of Massachusetts-Amherst, Amherst, Massachusetts 01003, USA.
J Am Soc Mass Spectrom. 2010 Mar;21(3):323-37. doi: 10.1016/j.jasms.2009.10.013. Epub 2009 Oct 29.
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.
质谱在生物制药行业中扮演着非常重要的角色，尽管它在蛋白质药物的开发、表征和质量控制中的应用主要局限于分析共价结构（氨基酸序列和翻译后修饰）。尽管蛋白质构象对于生物制药产品的生物活性、稳定性和安全性至关重要，但直到最近，用于探测生物聚合物的高级结构和构象动力学的基于质谱的方法的扩展武器库在该行业中并没有受到太多关注。由于最近的工作证明了这些实验工具在生物制药产品开发和制造的各个方面的实用性，这种情况正在开始改变。在这项工作中，我们使用一个典范的蛋白质药物干扰素 β-1a 作为示例，来说明质谱作为一种强大工具的实用性，不仅可以评估蛋白质药物的高级结构的完整性，还可以预测其在各种水平上降解的后果。
