Characterization of the structure and stability of human serum albumin isolated using a novel plasma extraction technique****
Characterization of the structure and stability of human serum albumin isolated using a novel plasma extraction technique****
批准号:
533721-2018
负责人:
Houry, Walid
金额:
$1.82万
依托单位:
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
项目状态:
已结题
起止时间:
2018-01-01 至 2019-12-31
中文摘要
分子伴侣是一组高度相互作用的细胞蛋白质,在蛋白质动态平衡的各个方面发挥中心作用,包括蛋白质折叠、组装和底物的展开。伴侣蛋白通常根据它们的序列相似性和功能被分为不同的家族。分子伴侣的另一个特征是在应激条件下抑制蛋白质聚集的能力。在这一点上,人血清白蛋白(HSA)就像是一种伴侣蛋白,阻止蛋白质聚集。人血清白蛋白是血浆中含量最丰富的蛋白质之一。它对游离脂肪酸、离子、胆盐和其他化合物的运输是必不可少的。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,在生理应激条件下,人血浆中HSA的耗尽会导致蛋白质聚集性的大幅增加。*在这项Engage项目中,Houry集团将与Evolve Biologics合作,以确定该公司独特的专有技术--‘PlamaCap EBATM’--产生的人血清白蛋白的结构和功能,该技术用于从血浆中提取蛋白质。与血浆产品行业的传统技术相比,这项新技术已经导致从每升捐赠者血浆中提取更多纯度更高的蛋白质。该项目代表着两个团队的自然合作,因为Houry团队使用最新的生化、生物物理和结构方法研究分子伴侣,而Evolve Biologics在血浆蛋白质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,如人血清白蛋白。因此,这种合作将在改善加拿大和世界各地依赖血浆蛋白疗法的人们的健康方面产生直接的翻译好处。
英文摘要
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.
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