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Macroion mobility spectrometer (IMS) for biochemical studies

Macroion mobility spectrometer (IMS) for biochemical studies
用于生化研究的宏离子迁移谱仪 (IMS)
批准号:
406200-2011
负责人:
Bearne, Stephen
金额:
$8.77万
依托单位:
依托单位国家:
加拿大
项目类别:
Research Tools and Instruments - Category 1 (<$150,000)
财政年份:
2010
资助国家:
加拿大
项目状态:
已结题
起止时间:
2010-01-01 至 2011-12-31

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中文摘要
翻译
蛋白质执行各种生物学功能,包括结构性功能(例如,蜘蛛丝),加速化学反应(酶),以及在血液中运输脂肪化合物的酶。 这些蛋白质通常折叠成离散的单位,这些单位相互作用形成复杂的(多聚体)结构:二聚体(2个单位),三聚体(3个单位),四聚体(4个单位)等。 CTP合酶催化遗传物质的结构单元的形成,并且是抗癌药物开发的公认靶标。 这种酶以无活性二聚体和活性四聚体的形式存在。 Bearne博士正在开发抑制这种酶的化合物,并需要评估是否因为化合物阻止四聚体形成而发生抑制。 他还在研究谷氨酸消旋酶,这种酶催化细菌细胞壁的构建块的形成,使其成为开发抗菌药物的目标。 Bearne博士已经发现了阻止这种酶形成活性二聚体的化合物。 这种酶不适合于评估其多聚体状态的传统方法。 所要求的宏离子迁移谱仪(IMS)将提供一种灵敏和快速的技术,以监测这两种酶的多聚体状态,并促进抑制剂的发展。 刘博士开发了一种生产人造蜘蛛丝的新方法--这种材料可能在伤口敷料和缝合线中找到医疗用途,并作为组织再生的支架。 IMS将允许刘博士评估这些蛋白质在形成丝之前是如何组装的,并且由于IMS的快速响应时间,他将能够真实的研究组装过程。 McLeod博士研究了肝脏中蛋白质与膳食脂肪的组装,IMS将使他能够测量这些复合物的大小,这似乎与它们引起心血管疾病的能力有关。 IMS的低样本要求和高灵敏度将使McLeod博士能够有效地利用他在实验室获得的宝贵而有限的血液样本。 他还将使用IMS来测量脂肪细胞中形成的蛋白质复合物的大小,这些蛋白质复合物在某些形式的糖尿病中很重要。
英文摘要
Proteins perform various biological functions including those that are structural (e.g., spider silk), that accelerate chemical reactions (enzymes), and those that transport fatty compounds in the blood. These proteins are often folded into discrete units which interact with each other to form complex (multimeric) structures: dimers (2 units), trimers (3 units), tetramers (4 units), etc. Dr. Bearne studies two enzymes that form such structures. The enzyme CTP synthase catalyzes the formation of a building block for genetic material and is a recognized target for the development of anticancer drugs. This enzyme exists as both an inactive dimer and an active tetramer. Dr. Bearne is developing compounds to inhibit this enzyme and needs to assess if the inhibition occurs because the compounds block tetramer formation. He is also studying the enzyme glutamate racemase that catalyzes the formation of a building block of bacterial cell walls, making it a target for the development of antibacterial drugs. Dr. Bearne has discovered compounds that prevent this enzyme from forming active dimers. This enzyme is not amenable to traditional methods of assessing its multimeric state. The requested macroIon Mobility Spectrometer (IMS) will provide a sensitive and rapid technique to monitor the multimeric state of these two enzymes and facilitate inhibitor development. Dr. Liu has developed a new method to produce artificial spider silk - a material that may find medical uses in wound dressings and sutures, and as scaffolds for tissue regeneration. An IMS will permit Dr. Liu to assess how these proteins assemble before forming silk and, because of the fast response time of the IMS, he will be able to study the assembly process in real time. Dr. McLeod studies the assembly of proteins with dietary fats in the liver and an IMS will allow him to measure the size of these complexes, which seems to be related to their ability to cause cardiovascular disease. The low sample requirement and high sensitivity of the IMS will allow Dr. McLeod to efficiently utilize the precious and limited blood samples he obtains in the lab. He will also use the IMS to measure the sizes of protein complexes formed in fat cells that are important in some forms of diabetes.
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    RGPIN-2016-05083
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