Characterization of the structure and stability of human serum albumin isolated using a novel plasma extraction technique****

使用新型血浆提取技术分离人血清白蛋白的结构和稳定性表征****

• 批准号: 533721-2018
• 负责人: Houry, Walid
• 金额: $ 1.82万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Engage Grants Program
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=653895
• 关键词: Characterization; structure; stability; human; serum

Molecular chaperones are a highly interactive group of cellular proteins that fulfill central roles in all aspects of protein homeostasis including protein folding, assembly, and unfolding of substrates. Chaperones are typically categorized into families based on their sequence similarity and function. Another characteristic feature of molecular chaperones is their ability to suppress protein aggregation under stress conditions. In this regard, human serum albumin (HSA) acts like a chaperone protein preventing protein aggregation. HSA is one of the most abundant proteins in blood plasma. It is essential for the transport of free fatty acids, ions, bile salts and other compounds. It is also required to maintain the colloidal osmotic pressure in the body and provides the majority of plasma anti-oxidant activity. Importantly, the depletion of HSA from human plasma results in a large increase in protein aggregation under physiological stress conditions. ****In this Engage project, the Houry group will collaborate with Evolve Biologics to characterize the structure and function of HSA generated by the company's unique proprietary technology, termed 'PlasmaCap EBATM', to extract proteins from blood plasma. This novel technique has resulted in the extraction of more proteins at higher purity from each liter of donor plasma as compared to the legacy technology in the plasma products industry. The project represents a natural collaboration for the two groups, since the Houry group studies molecular chaperones using the latest biochemical, biophysical, and structural approaches, while Evolve Biologics has extensive experience in plasma proteins. ****One of Evolve Biologics' priorities is in developing and commercializing well-established plasma protein therapeutics, such as HSA. Hence, this collaboration will have direct translational benefits in improving people's health in Canada and worldwide dependent on plasma protein therapeutics.

分子伴侣是一组高度相互作用的细胞蛋白质，在蛋白质稳态的所有方面发挥核心作用，包括蛋白质折叠，组装和底物的解折叠。伴侣通常基于它们的序列相似性和功能被分类为家族。分子伴侣的另一个特征是它们在应激条件下抑制蛋白质聚集的能力。在这方面，人血清白蛋白（HSA）就像一个伴侣蛋白防止蛋白质聚集。HSA是血浆中最丰富的蛋白质之一。它对于游离脂肪酸、离子、胆汁盐和其他化合物的运输至关重要。它还需要维持体内的胶体渗透压，并提供大部分血浆抗氧化活性。重要的是，从人血浆中消耗HSA导致在生理应激条件下蛋白质聚集的大幅增加。* 在这个Engage项目中，Houry集团将与Evolve Biologics合作，表征由该公司独特的专有技术“PlasmaCap EBATM”产生的HSA的结构和功能，以从血浆中提取蛋白质。与血浆制品行业的传统技术相比，这项新技术可以从每升供体血浆中提取更多、纯度更高的蛋白质。该项目代表了两个小组的自然合作，因为Houry小组使用最新的生物化学，生物物理和结构方法研究分子伴侣，而Evolve Biologics在血浆蛋白方面拥有丰富的经验。* Evolve Biologics的优先事项之一是开发和商业化成熟的血浆蛋白疗法，如HSA。因此，这项合作将在改善加拿大和全世界依赖血浆蛋白治疗的人们的健康方面产生直接的转化效益。