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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功能,包括结构功能(如蜘蛛丝)、加速化学反应的功能(酶)以及在血液中运输脂肪化合物的功能。这些蛋白质通常折叠成离散的单元,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。伯恩博士研究了形成这种结构的两种酶。CTP合成酶催化形成遗传物质的构建块,是开发抗癌药物的公认目标。这种酶以非活性二聚体和活性四聚体两种形式存在。伯恩博士正在开发抑制这种酶的化合物,需要评估这种抑制是否发生,因为这些化合物阻断了四聚体的形成。他还在研究谷氨酸消旋酶,这种酶能催化细菌细胞壁的形成,使其成为开发抗菌药物的目标。伯恩博士发现了能阻止这种酶形成活性二聚体的化合物。这种酶不能用传统的方法来评估它的多聚体状态。所要求的大离子迁移谱仪(IMS)将提供一种灵敏和快速的技术来监测这两种酶的多聚态,并促进抑制剂的开发。刘博士开发了一种生产人造蜘蛛丝的新方法,这种材料可以用于伤口敷料和缝合线,也可以用作组织再生的支架。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,他将能够实时研究组装过程。麦克劳德博士研究蛋白质与膳食脂肪在肝脏中的组合,而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和有限的血液样本。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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Critical Replacement of a Differential Scanning Calorimeter for Protein Studies
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    RGPIN-2016-05083
  • 项目类别:
    Discovery Grants Program - Individual
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