Harnessing the Promise of Negative Ion Electron Capture Dissociation (niECD) for Acidic Biomolecule Characterization

利用负离子电子捕获解离 (niECD) 进行酸性生物分子表征

• 批准号: 1609840
• 负责人: Kristina Hakansson
• 金额: $ 42万
• 依托单位: Regents of the University of Michigan - Ann Arbor
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1609840&HistoricalAwards=false
• 关键词: Harnessing; Promise; Negative; Ion; Electron

This award by the Chemical Measurement and Imaging (CMI) program supports work by Professor Kristina Håkansson and her group at the University of Michigan to explore new approaches to characterizing biomolecules using tandem mass spectrometry (MS/MS) - a powerful and sophisticated analytical tool. Specifically, the team has developed "negative ion electron capture dissociation (niECD)," a new approach to probing the structure of molecules. Their research aims to improve understanding of the fundamental mechanism of niECD, and to expand its applications to new classes of molecules that are difficult to characterize with conventional MS/MS approaches, with important implications for drug discovery and enhanced understanding of the molecular basis of living organisms. The work is providing training of graduate students in an interdisciplinary environment as well as participation in a K-12 Summer Program "Girls in Science and Engineering" offered by the University of Michigan's Women in Science and Engineering Program. The latter activities are aimed at boosting interest in the scientific method at a young age through the discovery that the contents of a box can be elucidated without opening it. This research seeks to explore the compatibility of niECD with a wider range of analytes that are difficult to characterize with conventional MS/MS approaches. Goals include investigation of a proposed zwitterion mechanism for the counter-intuitive niECD process, which results in charge-increased rather than the typical charge-decreased species in other ion-electron reactions, as well as further optimization of niECD for compatibility with liquid chromatography. Continued development of niECD will allow access to novel means for detailed structural characterization of important low-level acidic biomacromolecules such as phospho- and sulfopeptides, intact acidic proteins, cross-linked proteins, and RNA-small molecule complexes. Educational activities are aimed at boosting interest in the scientific method at a young age among htose underrepresented in science and engineering. The broader impact of the research includes introduction of novel technology for biomolecular structural characterization with important implications for drug discovery and an enhanced understanding of the molecular basis of living organisms.

该奖项由化学测量和成像 (CMI) 项目颁发，支持密歇根大学 Kristina Håkansson 教授及其团队的工作，探索使用串联质谱 (MS/MS)（一种强大而复杂的分析工具）表征生物分子的新方法。 具体来说，该团队开发了“负离子电子捕获解离（niECD）”，这是一种探测分子结构的新方法。 他们的研究旨在增进对 niECD 基本机制的理解，并将其应用扩展到难以用传统 MS/MS 方法表征的新分子类别，这对药物发现和增强对生物体分子基础的理解具有重要意义。 这项工作是在跨学科环境中为研究生提供培训，并让他们参与密歇根大学科学与工程女性项目提供的 K-12 夏季项目“科学与工程女孩”。 后者的活动旨在通过发现不打开盒子就可以阐明盒子里的东西来提高年轻时对科学方法的兴趣。 本研究旨在探索 niECD 与更广泛的分析物的兼容性，而这些分析物很难用传统的 MS/MS 方法进行表征。 目标包括研究反直觉 niECD 过程中提出的两性离子机制，该机制会导致其他离子电子反应中电荷增加而不是典型的电荷减少物质，以及进一步优化 niECD 以与液相色谱兼容。 niECD的持续开发将有助于获得新的方法来详细表征重要的低水平酸性生物大分子，例如磷酸肽和硫肽、完整酸性蛋白、交联蛋白和RNA-小分子复合物。 教育活动旨在提高科学和工程领域代表性不足的人年轻时对科学方法的兴趣。 该研究的更广泛影响包括引入生物分子结构表征新技术，这对药物发现具有重要意义，并增强了对生物体分子基础的理解。