INSTRUMENTATION FOR ANALYSIS OF HIGH MASS BIOMOLECULES

这项工作的目的是通过扩展其混合物分析能力和其有用的结构分析范围，从质量范围高达约2-4 kDa的分子到质量范围高达数十千道尔顿的分子，来推进生物分子的电喷雾/离子阱质谱的最新技术水平。 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）解离行为的基础因素的理解，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。 这项工作将允许应用程序被认为涉及直接询问，例如，整个蛋白质。 这样的应用可能包括快速蛋白质鉴定，翻译后修饰的快速鉴定，蛋白质变体的快速分析等。四极离子阱已经是一个非常强大的工具，用于生物衍生离子的操纵和质/荷分析。 这项工作将允许生物聚合物的大小急剧扩大，可以通过串联质谱与台式仪器进行研究。拟议的努力旨在开发新的工具，从高质量离子中获得结构信息，特别强调蛋白质。 将开发仪器，以便进行新的研究，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。 具体而言，新的仪器的发展，将提高离子/离子化学，可以研究的范围，并提高高质量离子的质量分析的优点的数字。

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.