INSTRUMENTATION FOR ANALYSIS OF HIGH MASS BIOMOLECULES

高质量生物分子分析仪器

• 批准号: 6604998
• 负责人: SCOTT A MCLUCKEY
• 金额: $ 22.16万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-01 至 2005-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6604998
• 关键词: biomedical equipment development; chemical association; electrospray ionization mass spectrometry; oligonucleotides; structural biology

The objective of this work is to advance the state-of-the-art in electrospray/ion trap mass spectrometry of biomolecules by extending its mixture analysis capabilities and its useful range of structural analysis from molecules ranging in mass up to about 2-4 kDa to molecules ranging in mass up to several tens of kiloDaltons. The two major emphasis areas in this work are to improve understanding of the factors that underlie the dissociation behavior of moderately sized proteins (less than 60 kDa) and to develop new experiments for complex bio-polymer mixture analysis based on ion/ion chemistry. This work will permit applications to be considered that involve the direct interrogation of, for example, whole proteins. Such applications might include rapid protein identification, rapid identification of post-translational modifications, rapid analysis of protein variants, etc. The quadrupole ion trap is already a remarkably powerful tool for the manipulation and mass/charge analysis of biologically-derived ions. This work will allow for a dramatic expansion in the size of bio-polymer that can be studied via tandem mass spectrometry with a bench-top instrument. The proposed effort seeks to develop new tools for deriving structural information from high mass ions, with particular emphasis on proteins. Instrumentation will be developed to allow for new studies designed to improve understanding of the ion/ion reactions of proteins and the unimolecular (i.e. dissociation) reactions of proteins. Specifically, new instrumental developments will be made to enhance both the range of ion/ion chemistry that can be studied and to improve the figures of merit of mass analysis of high mass ions.

这项工作的目的是通过扩展其混合物分析能力及其有用的结构分析范围（从质量高达约 2-4 kDa 的分子到质量高达几十千道尔顿的分子）来推进生物分子电喷雾/离子阱质谱的最先进水平。 这项工作的两个主要重点领域是提高对中等大小蛋白质（小于 60 kDa）解离行为背后因素的理解，并开发基于离子/离子化学的复杂生物聚合物混合物分析的新实验。 这项工作将允许考虑涉及直接询问例如完整蛋白质的应用。 此类应用可能包括快速蛋白质鉴定、快速鉴定翻译后修饰、快速分析蛋白质变体等。四极离子阱已经是用于生物衍生离子的操作和质/荷分析的非常强大的工具。 这项工作将使生物聚合物的尺寸急剧扩大，可以通过台式仪器的串联质谱法进行研究。拟议的工作旨在开发新工具，从高质量离子中获取结构信息，特别是蛋白质。 将开发仪器以进行新的研究，旨在提高对蛋白质的离子/离子反应和蛋白质的单分子（即解离）反应的理解。 具体来说，将开发新的仪器，以扩大可研究的离子/离子化学的范围，并提高高质量离子的质量分析的品质因数。