EAGER: Therapeutic Protein Separations via Surface Isoelectric Focusing (sIEF)

1548107密歇根理工大学Minerick这一年，ENGING将探索一种新的、具有潜在变革意义的小体积蛋白质分离方法，称为表面等电聚焦(Sef)。Sef通过操作比以前的IEF技术小100倍的操作，提供了更简单、更便宜、更快和更灵敏的分析的可能性。这项研究将扩展等电聚焦方面的知识，以非常高的分辨率分离和识别两性分子，例如蛋白质，这是涉及蛋白质异常的蛋白质病的医学诊断和治疗性蛋白质的药物筛选的基础。在临床上，较大规模的平板凝胶中的IEF是资源、劳动力和时间密集型的，正在被较小的体积、基因组和亲和力方法所取代。治疗性蛋白质的糖基化工程已被证明可以改善分子稳定性，调节理化和药理学特性，并改善药物动力学，具有更好的吸收、更长的循环时间和更低的清除率。这项工作可能产生必要的知识，导致Sef工具的开始，该工具可以与治疗性蛋白质库无缝对接。其结果将是快速筛选和有价值的电荷和等电点信息，以帮助开发治疗性蛋白质。

1548107Michigan Technological UniversityMinerickThis one year EAGER will explore a new and potentially transformative approach to small volume protein separations called surface isoelectric focusing (sIEF). sIEF offers the potential for simpler, cheaper, quicker, and sensitive analysis by operating 100 times smaller than previous IEF techniques. This research will expand knowledge in isoelectric focusing to separate and identify amphoteric molecules, e.g., proteins, at very high resolution, which is fundamental to medical diagnostics of proteopathy diseases involving protein abnormalities and pharmaceutical screening of therapeutic proteins. IEF in larger scale slab gels is resource, labor, and time intensive being replaced clinically by smaller volume, genomic and affinity approaches. Glycoengineering of therapeutic proteins has been shown to improve molecular stability, regulate physicochemical and pharmacological properties, and improve pharmacokinetics with better absorption, longer circulation times, and decreased clearance rates. This work could produce the knowledge necessary to lead to the beginning of an sIEF tool which could interface seamlessly with therapeutic protein libraries. The result would be rapid screening and valuable charge and isoelectric point information to aid with the development of therapeutic proteins.