Advances and challenges in analytical characterization of biotechnology products: mass spectrometry-based approaches to study properties and behavior of protein therapeutics.
Advances and challenges in analytical characterization of biotechnology products: mass spectrometry-based approaches to study properties and behavior of protein therapeutics.
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DOI：
10.1016/j.biotechadv.2011.05.006
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发表时间：
2012-01
影响因子：
16
通讯作者：
Wang, Shunhai
中科院分区：
文献类型：
--
作者：
Kaltashov, Igor A.;Bobst, Cedric E.;Abzalimov, Rinat R.;Wang, Guanbo;Baykal, Burcu;Wang, Shunhai
关键词：
生物制药是一类独特的药物，由于其极端的结构复杂性。这些治疗性蛋白的结构对其有效性和安全性至关重要，在不同水平（从序列到构象）表征它的能力不仅在质量控制阶段至关重要，而且在整个发现和设计阶段也至关重要。生物质谱（MS）为研究复杂蛋白质药物的结构和行为提供了多种方法，并且已经成为表征蛋白质治疗药物共价结构的默认工具，包括序列和翻译后修饰。最近，以ms为基础的方法作为提供生物技术产品的高阶结构和动态信息的一种手段，也开始受到广泛的欢迎。特别是氢/氘交换质谱和电喷雾电离（ESI）质谱中蛋白质离子的电荷态分布分析为评估蛋白质构象的完整性提供了方便的方法。原生ESI质谱还允许使用简单的模型系统监测蛋白质药物与其治疗靶点和其他生理伙伴的相互作用。基于质谱的方法也被应用于研究生物制药产品的药代动力学，在这方面它们开始与传统的免疫分析相竞争。质谱已经为生物制药开发的各个阶段提供了宝贵的支持，从发现到批准后的监测，它对生物制药分析领域的影响无疑将继续增长。
Biopharmaceuticals are a unique class of medicines due to their extreme structural complexity. The structure of these therapeutic proteins is critically important for their efficacy and safety, and the ability to characterize it at various levels (from sequence to conformation) is critical not only at the quality control stage, but also throughout the discovery and design stages. Biological mass spectrometry (MS) offers a variety of approaches to study structure and behavior of complex protein drugs and has already become a default tool for characterizing the covalent structure of protein therapeutics, including sequence and post-translational modifications. Recently, MS-based methods have also begun enjoying a dramatic growth in popularity as a means to provide information on higher order structure and dynamics of biotechnology products. In particular, hydrogen/deuterium exchange MS and charge state distribution analysis of protein ions in electrospray ionization (ESI)MS offer a convenient way to assess the integrity of protein conformation. Native ESI MS also allows the interactions of protein drugs with their therapeutic targets and other physiological partners to be monitored using simple model systems. MS-based methods are also applied to study pharmacokinetics of biopharmaceutical products, where they begin to rival traditional immunoassays. MS already provides valuable support to all stages of development of biopharmaceuticals, from discovery to post-approval monitoring, and its impact on the field of biopharmaceutical analysis will undoubtedly continue to grow.
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影响因子：
7.4
作者：
Abzalimov, Rinat R.;Dubin, Paul L.;Kaltashov, Igor A.
通讯作者：
Kaltashov, Igor A.
DOI：
10.1016/j.jasms.2006.06.006
发表时间：
2006-11-01
影响因子：
3.2
作者：
Englander, S. Walter
通讯作者：
Englander, S. Walter
影响因子：
7.4
作者：
Bagal, Dhanashri;Zhang, Heidi;Schnier, Paul D.
通讯作者：
Schnier, Paul D.
影响因子：
64.5
作者：
Cheng, Y;Zak, O;Walz, T
通讯作者：
Walz, T
影响因子：
4.4
作者：
Chrisman, PA;McLuckey, SA
通讯作者：
McLuckey, SA