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Hydration-Induced Structural Changes in the Solid State of Protein: A SAXS/WAXS Study on Lysozyme.
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2020-08-05 , DOI: 10.1021/acs.molpharmaceut.0c00351 Tuan Phan-Xuan 1, 2, 3 , Ekaterina Bogdanova 1, 2 , Anna Millqvist Fureby 4 , Jonas Fransson 5 , Ann E Terry 3 , Vitaly Kocherbitov 1, 2
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2020-08-05 , DOI: 10.1021/acs.molpharmaceut.0c00351 Tuan Phan-Xuan 1, 2, 3 , Ekaterina Bogdanova 1, 2 , Anna Millqvist Fureby 4 , Jonas Fransson 5 , Ann E Terry 3 , Vitaly Kocherbitov 1, 2
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The stability of biologically produced pharmaceuticals is the limiting factor to various applications, which can be improved by formulation in solid-state forms, mostly via lyophilization. Knowledge about the protein structure at the molecular level in the solid state and its transition upon rehydration is however scarce, and yet it most likely affects the physical and chemical stability of the biological drug. In this work, synchrotron small- and wide-angle X-ray scattering (SWAXS) are used to characterize the structure of a model protein, lysozyme, in the solid state and its structural transition upon rehydration to the liquid state. The results show that the protein undergoes distortion upon drying to adopt structures that can continuously fill the space to remove the protein–air interface that may be formed upon dehydration. Above a hydration threshold of 35 wt %, the native structure of the protein is recovered. The evolution of SWAXS peaks as a function of water content in a broad range of concentrations is discussed in relation to the structural changes in the protein. The findings presented here can be used for the design and optimization of solid-state formulations of proteins with improved stability.
中文翻译：
水合诱导的蛋白质固态结构变化：溶菌酶的SAXS / WAXS研究。
生物生产的药物的稳定性是各种应用的限制因素，可以通过以固态形式配制（主要是通过冻干）来改善这种稳定性。然而，关于固态分子结构的蛋白质及其在水合后的转变的知识很少，但是很可能会影响生物药物的物理和化学稳定性。在这项工作中，同步加速器小角度和广角X射线散射（SWAXS）用于表征固体状态下的模型蛋白溶菌酶的结构及其在重新水合为液态时的结构转变。结果表明，蛋白质在干燥后会发生变形，从而采用可以连续填充空间的结构，从而消除可能因脱水而形成的蛋白质-空气界面。超过35wt％的水合阈值，就恢复了蛋白质的天然结构。在蛋白质的结构变化方面，讨论了SWAXS峰在宽浓度范围内随水分含量变化的变化。本文介绍的发现可用于设计和优化具有改进稳定性的蛋白质固态制剂。
更新日期：2020-09-09
中文翻译：
水合诱导的蛋白质固态结构变化：溶菌酶的SAXS / WAXS研究。
生物生产的药物的稳定性是各种应用的限制因素，可以通过以固态形式配制（主要是通过冻干）来改善这种稳定性。然而，关于固态分子结构的蛋白质及其在水合后的转变的知识很少，但是很可能会影响生物药物的物理和化学稳定性。在这项工作中，同步加速器小角度和广角X射线散射（SWAXS）用于表征固体状态下的模型蛋白溶菌酶的结构及其在重新水合为液态时的结构转变。结果表明，蛋白质在干燥后会发生变形，从而采用可以连续填充空间的结构，从而消除可能因脱水而形成的蛋白质-空气界面。超过35wt％的水合阈值，就恢复了蛋白质的天然结构。在蛋白质的结构变化方面，讨论了SWAXS峰在宽浓度范围内随水分含量变化的变化。本文介绍的发现可用于设计和优化具有改进稳定性的蛋白质固态制剂。
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