# Hybrid structural mass spectrometry for rapid site-specific glycan structural elucidation

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2021 · $426,668

## Abstract

PROJECT SUMMARY
 An extensive array of glycosylation covers the extracellular milieu of higher level organisms. These
glycan structures are attached to half of the human proteome and are critical for their function in nearly all
biological processes. Monitoring alterations in the structures of glycosylation on glycolipids and glycoproteins
can identify new ways of inhibiting infections and pinpoint new targets for detecting and treating autoimmune
diseases and cancer. Despite their biological importance, our ability to monitor the vast array of glycan
structures and their exact role in disease states remains limited. This is primarily due to the challenges
associated with analyzing complex carbohydrate structures, which present an unparalleled level of structural
diversity. Tools for large-scale glycomic studies do not provide the level of structural detail necessary to
effectively resolve subtle differences in glycan structures. On the other hand, techniques capable of detailed
structural elucidation of glycans are slow, experimentally intensive, and often require multiple approaches. This
proposal seeks to develop an analytical platform that will enable rapid glycan characterization with a level of
structural detail that is unavailable with existing techniques.
 This proposal aims to incorporate ion mobility (IMS) and gas-phase hydrogen/deuterium exchange
(HDX) for glycan structural analysis into a robust mass spectrometry platform. We will use this platform with
novel internal standards to analyze a library of monosaccharides, oligosaccharides, glycan chains from
glycoproteins, and glycolipids to assemble a database of the ion mobility (Aim 1) and hydrogen/deuterium
exchange (Aim 2) properties of biologically relevant carbohydrate ions. Molecular modeling will be used to help
interpret and rationalize the different behaviors of each structure and expand our structural reference database
in silico (Aim 3). The combination of ion mobility and hydrogen/deuterium exchange will be implemented into a
LC-MS platform for Glycan Structural Elucidation on a Chromatographic Timescale “GlySECT” (Aim 4). In
parallel, we will develop the software for extracting the data and searching against the databases established
in this project to aid in structural elucidation of the glycan chains. This technology has the potential to enable
rapid, site-specific, glycan structural determination and provide a much-needed tool for glycobiology, biomarker
discovery, and therapeutic protein characterization.

## Key facts

- **NIH application ID:** 10186777
- **Project number:** 5R01GM127579-04
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Miklos Guttman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $426,668
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10186777

## Citation

> US National Institutes of Health, RePORTER application 10186777, Hybrid structural mass spectrometry for rapid site-specific glycan structural elucidation (5R01GM127579-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10186777. Licensed CC0.

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