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Carbohydrates and glycans are integral to many biological processes, including cell-cell recognition and energy storage. However, carbohydrates are often difficult to analyze due to the high degree of isomerism present. One method being developed to distinguish these isomeric species is hydrogen/deuterium exchange-mass spectrometry (HDX-MS). In HDX-MS, carbohydrates are exposed to a deuterated reagent and the functional groups with labile hydrogen atoms, including hydroxyls and amides, exchange with the 1 amu heavier isotope, deuterium. These labels can then be detected by MS, which monitors the mass increase with the addition of D-labels. The observed rate of exchange is dependent on the exchanging functional group, the accessibility of the exchanging functional group, and the presence of hydrogen bonds. Herein, we discuss how HDX has been applied in the solution-phase, gas-phase, and during MS ionization to label carbohydrates and glycans. Additionally, we compare differences in the conformations that are labeled, the labeling timeframes, and applications of each of these methods. Finally, we comment on future opportunities for development and use of HDX-MS to analyze glycans and glycoconjugates.
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Metal adduction in mass spectrometric analyses of carbohydrates and glycoconjugates
Glycans, carbohydrates, and glycoconjugates are involved in many crucial biological processes, such as disease development, immune responses, and cell-cell recognition. Glycans and carbohydrates are known for the large number of isomeric features associated with their structures, making analysis challenging compared with other biomolecules. Mass spectrometry has become the primary method of structural characterization for carbohydrates, glycans, and glycoconjugates. Metal adduction is especially important for the mass spectrometric analysis of carbohydrates and glycans. Metal-ion adduction to carbohydrates and glycoconjugates affects ion formation and the three-dimensional, gas-phase structures. Herein, we discuss how metal-ion adduction impacts ionization, ion mobility, ion activation and dissociation, and hydrogen/deuterium exchange for carbohydrates and glycoconjugates. We also compare the use of different metals for these various techniques and highlight the value in using metals as charge carriers for these analyses. Finally, we provide recommendations for selecting a metal for analysis of carbohydrate adducts and describe areas for continued research.
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- Award ID(s):
- 1945078
- PAR ID:
- 10399790
- Date Published:
- Journal Name:
- Mass Spectrometry Reviews
- ISSN:
- 0277-7037
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1002/mas.21801
