Mass spectrometry of proteins

本提案旨在研究质谱法在蛋白质研究中的应用。质谱仪是用来检测和鉴定微量物质的科学仪器。在质谱仪中，分子带电形成“离子”，然后根据它们的质量与电荷的比率在真空中分离离子。直到最近才有可能制造出像血红蛋白这样的大蛋白分子的离子，并将它们注入真空中。这里提出的基本工作将检查真空中蛋白质离子的特性，并将它们与溶液中蛋白质的特性进行比较，在溶液中它们执行正常的生物功能。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，那么质谱仪可以用来研究蛋白质与其他物种的结合，以一种快速，敏感的特定方式。具体来说，我们将研究血红蛋白离子的特性，以及导致疾病的血红蛋白突变对这些特性的影响。一类被称为“分子伴侣”的小分子药物在真空中与蛋白质结合的特性将被研究。质谱法可能提供一种鉴定伴侣分子的新方法。二氧化碳与血红蛋白等蛋白质的反应将被研究。长期以来，人们一直认为这是血液中二氧化碳运输的一种可能方法，但尚未详细量化。最后，我们将研究在蛋白质离子中加入一定量的水分子的影响，以确定对蛋白质离子折叠的影响。这项工作将为研究蛋白质在医学、制药和生物技术中的应用带来新的方法。加拿大将至少在两个方面受益。这项工作将在一个对高素质人才有强烈需求的领域培养学生和博士后。任何知识产权将归英属哥伦比亚大学所有，因此将留在加拿大。

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.