Mass spectrometry of proteins

蛋白质质谱分析

• 批准号: 227465-2010
• 负责人: Douglas, Donald
• 金额: $ 3.64万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2012
• 资助国家: 加拿大
• 起止时间: 2012-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=514263
• 关键词: Mass; spectrometry; proteins

This proposal is for research in mass spectrometry applied to the study of proteins. Mass spectrometers are scientific instruments used to detect and identify trace substances. In mass spectrometers, molecules are electrically charged to form "ions" and the ions are then separated in vacuum according to their ratios of mass to charge. Only recently has it become possible to make ions of large protein molecules, like hemoglobin, and inject them into vacuum. The fundamental work proposed here will examine the properties of ions of proteins in vacuum and compare them to the properties of the proteins in solution, where they carry out their normal biological functions. In some cases, proteins in a vacuum can retain their solution properties. If this is generally true, then mass spectrometers can be uses to study binding of proteins to other species in a fast, sensitive specific way. Specifically we will examine the properties of hemoglobin ions, and the effects on these properties of mutations to Hb that cause disease. The properties of a class of small-molecule drugs called "molecular chaperones" binding to proteins in vacuum will be investigated. Mass spectrometry may provide a new method to identify chaperone molecules. The reaction of carbon dioxide with proteins like hemoglobin will be studied. This has long been known to be a possible method of transport of CO2 in blood, but has not been quantified in detail. Finally we will investigate the effects of adding controlled numbers of water molecules to protein ions, to determine the effects on folding of the protein ions. This work will lead to new approaches to study proteins for applications in medicine, pharmacy and biotechnology. Canada will benefit in at least two ways. The proposed work will train students and postdoctoral fellows in a field where there is a strong demand for such highly qualified personnel. Any intellectual property will be owned by the University of British Columbia, and thus will remain in Canada.

本提案是用于研究蛋白质的质谱法的研究。质谱仪是用于检测和识别痕量物质的科学仪器。在质谱仪中，分子被充电以形成“离子”，然后离子根据它们的质荷比在真空中分离。直到最近，才有可能制造出大蛋白质分子（如血红蛋白）的离子，并将它们注入真空。这里提出的基本工作将检查蛋白质离子在真空中的性质，并将其与溶液中蛋白质的性质进行比较，在溶液中蛋白质执行其正常的生物功能。在某些情况下，真空中的蛋白质可以保持其溶液性质。如果这通常是正确的，那么可以使用质谱仪以快速、灵敏的特定方式研究蛋白质与其他物种的结合。具体来说，我们将研究血红蛋白离子的性质，以及导致疾病的血红蛋白突变对这些性质的影响。将研究一类称为“分子伴侣”的小分子药物在真空中与蛋白质结合的性质。质谱法可能为分子伴侣的鉴定提供一种新的方法。将研究二氧化碳与血红蛋白等蛋白质的反应。长期以来，人们一直认为这是一种可能的血液中CO2运输方法，但尚未详细量化。最后，我们将研究向蛋白质离子中加入受控数量的水分子的影响，以确定对蛋白质离子折叠的影响。这项工作将导致新的方法来研究蛋白质在医学，制药和生物技术中的应用。中国至少在两个方面受益。拟议的工作将在一个对这种高素质人才有强烈需求的领域培训学生和博士后研究员。任何知识产权将由不列颠哥伦比亚省大学拥有，因此将留在加拿大。