High Resolution Superficially Porous Materials for Native Protein Separations

用于天然蛋白质分离的高分辨率表面多孔材料

• 批准号: 10255623
• 负责人: Barry E Boyes
• 金额: $ 27.97万
• 依托单位: ADVANCED MATERIALS TECHNOLOGY, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10255623
• 关键词: Address; Antibody-drug conjugates; Architecture; Biological; Biological Process; Biological Products; Biological Sciences; Biomedical Research; Caliber; Characteristics; Chemistry; Chromatography; Complex; Development; Ethylene Oxide; Evaluation; Future; Glycopeptides; Glycoproteins; Goals; Heterogeneity; High Pressure Liquid Chromatography; Hour; Hydrophobic Interactions; Ion Exchange; Knowledge; Lead; Libraries; Liquid Chromatography; Liquid substance; Literature; Measurable; Measurement; Measures; Methods; Modification; Molecular; Molecular Conformation; Outcome; Particle Size; Peptides; Performance; Pharmaceutical Preparations; Phase; Polysaccharides; Preparation; Property; Protein Analysis; Protein Isoforms; Proteins; Quality Control; Reaction; Recombinant Proteins; Research; Resolution; Safety; Sampling; Savings; Science; Silicon Dioxide; Speed; Structure; Surface; System; Technology; Therapeutic; Therapeutic Intervention; Therapeutic Monoclonal Antibodies; Thick; Time; Variant; Work; analytical method; comparative; design; drug development; experience; improved; interest; materials science; next generation; novel; operation; particle; product development; quality assurance; success; therapeutic protein

Abstract Life sciences research and other critical bioanalytical applications would strongly benefit from faster and higher resolution high performance liquid chromatographic (HPLC) separations of larger molecules including proteins, peptides, glycopeptides, and glycans. Proteins therapeutics are complex molecules, susceptible to intended or unintended alterations of composition and conformation. Many therapeutic proteins are inherently a mixture of closely related variants. Current practice is to employ HPLC to resolve and quantify the components such protein mixtures, to assure identity and safety of the protein drug. Many HPLC separations of proteins are limited in resolution of protein mixtures, require an hour or more, and may not completely resolve all of the components. Due to the complexity of samples, there are many examples in the current research literature that combine multiple HPLC analyses to gain full details on protein composition, and to measure the levels of protein variants, both during development of the drug, as well as manufacture and quality assurance/quality control. Regardless of the intended use of the quantitative information, high efficiency LC separations are a fundamental part of the analytical systems, and the time to achieve high resolution separations of protein samples is a great bottleneck. This proposal describes an approach to improve the separation efficiency of HPLC for protein analysis by extending the use of novel superficially porous particle (SPP) technologies with optimized characteristics, providing significantly faster and higher resolution separations of proteins in the native state. Our objectives are to create SPP silica particles, specifically design for use in conditions that maintain intact native structures, optimize the materials properties, and to load these materials efficiently into HPLC column formats. The proposed work will extend recent breakthroughs in material science that yield authentic improvements in current materials, seeking to employ the technology in additional native modes of HPLC operation, including hydrophobic interaction and ion exchange. The goals of the proposed work would yield very high performance chromatographic products, greater than those currently available, to be applied broadly in analysis of proteins, particularly for protein therapeutics. The application of the technology is not limited to biopharmaceutical preparations, and, in fact, would benefit any current application that uses HPLC methods for larger biological molecule analyses. The separations technology described will directly lead to useful products for which there is a significant technical and market demand.

抽象的 生命科学研究和其他关键的生物分析应用将大大受益 更快，更高的分辨率高性能液相色谱（HPLC）较大的分离 包括蛋白质，肽，糖肽和聚糖在内的分子。蛋白质疗法很复杂 分子，易受组成和构象的意图改变或意外变化。许多 治疗蛋白本质上是密切相关变体的混合物。当前的做法是雇用 HPLC解决和量化此类蛋白质混合物的成分，以确保身份和安全性 蛋白质药物。蛋白质的许多HPLC分离有限于蛋白质混合物的分辨率， 需要一个小时或更长时间，并且可能无法完全解决所有组件。由于复杂性 在样本中，当前研究文献中有许多示例结合了多个HPLC 分析以获取有关蛋白质成分的完整详细信息，并测量蛋白质变异的水平 在开发药物以及制造和质量保证/质量控制期间。 不管定量信息的预期使用如何，高效LC分离是一个 分析系统的基本部分，以及实现高分辨率分离的时间 蛋白质样品是一个很好的瓶颈。该建议描述了一种改善分离的方法 HPLC对蛋白质分析的效率通过扩展新型多孔粒子的使用来进行蛋白质分析 （SPP）具有优化特性的技术，可显着更快，更高的分辨率 蛋白质在本地状态的分离。我们的目标是创建SPP二氧化硅颗粒， 专门设计用于维持完整天然结构的条件，优化材料 属性，并有效地加载这些材料为HPLC柱格式。拟议的工作将 扩展了材料科学的最新突破，从而产生当前的真实改善 材料，试图在HPLC操作的其他本机模式下采用该技术，包括 疏水相互作用和离子交换。拟议工作的目标将产生很高 性能色谱产品，大于当前可用的产品，可广泛应用 在蛋白质分析中，特别是针对蛋白质疗法。该技术的应用不是 仅限于生物制药的准备工作，实际上，将受益于当前使用的任何应用程序 用于较大生物分子分析的HPLC方法。所描述的分离技术将 直接导致有很大的技术和市场需求的有用产品。