Characterizing Protein Structure, Dynamics and Conformation in Lyophilized Solids
Characterizing Protein Structure, Dynamics and Conformation in Lyophilized Solids
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DOI：
10.2174/1381612821666151008150735
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发表时间：
2015-01-01
影响因子：
3.1
通讯作者：
Topp, Elizabeth M.
中科院分区：
文献类型：
--
作者：
Moorthy, Balakrishnan S.;Iyer, Lavanya K.;Topp, Elizabeth M.
固态蛋白质治疗剂的长期稳定性取决于冻干过程中和冻干粉末中天然结构的保存。蛋白质在冻干时可以可逆或不可逆地展开，获得在储存期间容易降解的构象。因此，表征干燥状态的蛋白质对于设计安全有效的配方至关重要。本综述总结了常用于表征冻干固体中蛋白质结构、动力学和构象的分析技术的基本原理和应用。该综述还讨论了最近开发的基于质谱的方法（固态氢氘交换质谱（ssHDX-MS）和固态光解标记质谱（ssPL-MS））的应用及其以高分辨率研究固态蛋白质的能力。
The long-term stability of protein therapeutics in the solid-state depends on the preservation of native structure during lyophilization and in the lyophilized powder. Proteins can reversibly or irreversibly unfold upon lyophilization, acquiring conformations susceptible to degradation during storage. Therefore, characterizing proteins in the dried state is crucial for the design of safe and efficacious formulations. This review summarizes the basic principles and applications of the analytical techniques that are commonly used to characterize protein structure, dynamics and conformation in lyophilized solids. The review also discusses the applications of recently developed mass spectrometry based methods (solid-state hydrogen deuterium exchange mass spectrometry (ssHDX-MS) and solid-state photolytic labeling mass spectrometry (ssPL-MS)) and their ability to study proteins in the solid-state at high resolution.