With support from the Chemical Measurement and Imaging Program in the Division of Chemistry, Professor Benjamin Bythell and his group at the University of Missouri-St. Louis is developing new tools for determining the structure of complex sugars known as "glycans." The complexity of glycans makes their analysis challenging, but their pervasiveness in biology makes their characterization important. The primary difficulty comes from the fact that subtle differences in the assembly of similar components can make large structural and - importantly - functional differences. The Bythell group is using tandem mass spectrometry (a powerful technology for determining molecular structure and sample composition) combined with computational modeling to enable screening and identification of unknown glycans without the need for synthetic standards. Resulting savings of time and money can advance the pace of discoveries impacting areas such as medical and pharmaceutical interventions. The work provides interdisciplinary research opportunities for undergraduate, graduate, and high-school students, including members of underrepresented groups.
A key aim of this research is to understand how sequence information can be recovered following mass spectrometric fragmentation of glycans. The PI seeks to predict ratios of fragment ions based on the energetics of the transition and the structures of the products. Combining these two capabilities will enable prompt generation of predicted spectra for comparison with experiments. The approach uses computational methods combined with tandem mass spectrometry of regioselectively labeled and sodiated glycan model compounds. Improved understanding of fragmentation chemistry will provide greater confidence in assignment of glycan ion structures and prediction of relative abundance, leading to faster and more accurate identification of glycan sequences and glycosidic bonding arrangements without the need for synthetic standards.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
