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

化学测量和成像（CMI）计划的这一奖项支持密歇根大学的Kristina Håkansson教授及其团队的工作，以探索使用串联质谱（MS/MS）表征生物分子的新方法-一种强大而复杂的分析工具。 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。 他们的研究旨在提高对niECD基本机制的理解，并将其应用扩展到难以用常规MS/MS方法表征的新分子类别，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对研究生进行培训，并参加密歇根大学妇女参与科学和工程方案提供的K-12暑期方案“科学和工程女孩”。 后者的活动旨在通过发现一个盒子的内容可以在不打开它的情况下阐明，从而提高年轻人对科学方法的兴趣。这项研究旨在探索niECD与更广泛的分析物的兼容性，这些分析物难以用传统的MS/MS方法进行表征。 目标包括调查提出的反直觉的niECD过程中，这导致在电荷增加，而不是典型的电荷减少的物种在其他离子-电子反应，以及进一步优化niECD与液相色谱的兼容性的两性离子交换机理。 niECD的持续发展将允许获得用于重要的低水平酸性生物大分子的详细结构表征的新手段，所述低水平酸性生物大分子例如磷酸肽和磺基肽、完整酸性蛋白、交联蛋白和RNA-小分子复合物。 教育活动的目的是在科学和工程领域代表性不足的年轻人中提高对科学方法的兴趣。 该研究的更广泛影响包括引入生物分子结构表征的新技术，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。

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.