An Evaluation of the Potential of NMR Spectroscopy and Computational Modelling Methods to Inform Biopharmaceutical Formulations.
An Evaluation of the Potential of NMR Spectroscopy and Computational Modelling Methods to Inform Biopharmaceutical Formulations.
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DOI：
10.3390/pharmaceutics10040165
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发表时间：
2018-09-21
期刊：
影响因子：
5.4
通讯作者：
Dalby PA
中科院分区：
文献类型：
--
作者：
Pandya A;Howard MJ;Zloh M;Dalby PA
基于蛋白质的治疗剂被认为是市场上最重要的药物类别之一。事实证明，延长液态高蛋白浓度的稳定性这一日益增长的需求具有挑战性。因此，人们正在付出巨大努力来设计配方，以使这些高浓度蛋白质治疗剂能够储存长达2年。目前，辅料选择方法涉及经验性的高通量筛选，但没有揭示在储存条件下聚集机制或配方的分子水平效应的细节。计算建模方法有可能阐明这些机制，并在实验测试之前进行计算机模拟快速筛选。核磁共振（NMR）光谱也能为辅料 - 蛋白质相互作用提供补充性见解。本综述将强调分子建模和NMR光谱的基本原理。它还将讨论计算方法和NMR方法在研究辅料 - 蛋白质相互作用的应用方面的进展。
Protein-based therapeutics are considered to be one of the most important classes of pharmaceuticals on the market. The growing need to prolong stability of high protein concentrations in liquid form has proven to be challenging. Therefore, significant effort is being made to design formulations which can enable the storage of these highly concentrated protein therapies for up to 2 years. Currently, the excipient selection approach involves empirical high-throughput screening, but does not reveal details on aggregation mechanisms or the molecular-level effects of the formulations under storage conditions. Computational modelling approaches have the potential to elucidate such mechanisms, and rapidly screen in silico prior to experimental testing. Nuclear Magnetic Resonance (NMR) spectroscopy can also provide complementary insights into excipient–protein interactions. This review will highlight the underpinning principles of molecular modelling and NMR spectroscopy. It will also discuss the advancements in the applications of computational and NMR approaches in investigating excipient–protein interactions.
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