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

Regents Of The University Of Michigan - Ann Arbor, Ann Arbor MI

Investigators

Abstract

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.