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

这项由化学测量和成像(CMI)项目颁发的奖项支持密歇根大学的Kristina Hakansson教授和她的团队探索使用串联质谱仪(MS/MS)表征生物分子的新方法--这是一种强大而复杂的分析工具。具体地说，该团队开发了一种新的探测分子结构的方法--负离子电子俘获解离(NiECD)。他们的研究旨在提高对NiECD基本机制的理解，并将其应用于传统MS/MS方法难以表征的新型分子，对药物开发和加深对活体生物分子基础的理解具有重要意义。这项工作是为研究生提供跨学科环境的培训，以及参加由密歇根大学女性科学与工程项目提供的K-12暑期项目“科学与工程女孩”。后一项活动的目的是在年轻的时候通过发现盒子里的东西可以在不打开的情况下被阐明来提高人们对科学方法的兴趣。这项研究试图探索NiECD与更广泛的分析物的兼容性，这些分析物很难用传统的MS/MS方法进行表征。目标包括研究提出的反直觉NiECD过程的两性离子机制，该过程导致电荷增加，而不是其他离子-电子反应中典型的电荷减少物种，以及进一步优化NiECD与液相色谱的兼容性。NiECD的继续开发将使人们能够获得新的手段，用于详细描述重要的低水平酸性生物大分子的结构，如磷酸和磺酸肽、完整的酸性蛋白质、交联蛋白质和RNA-小分子复合体。教育活动的目的是在科学和工程学中代表性不足的人中，在年轻时提高对科学方法的兴趣。这项研究的更广泛影响包括引入对药物发现具有重要影响的生物分子结构表征的新技术，以及加强对生物有机体分子基础的了解。

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.