Biomimetic reagents for the selective free radical and acid-base chemistry of glycans: Application to glycan structure determination by mass spectrometry

Jinshan Gao, Daniel A. Thomas, Chang Ho Sohn, J. L. Beauchamp

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Nature excels at breaking down glycans into their components, typically via enzymatic acid-base catalysis to achieve selective cleavage of the glycosidic bond. Noting the importance of proton transfer in the active site of many of these enzymes, we describe a sequestered proton reagent for acid-catalyzed glycan sequencing (PRAGS) that derivatizes the reducing terminus of glycans with a pyridine moiety possessing moderate proton affinity. Gas-phase collisional activation of PRAGS-derivatized glycans predominately generates C1-O glycosidic bond cleavages retaining the charge on the reducing terminus. The resulting systematic PRAGS-directed deconstruction of the glycan can be analyzed to extract glycan composition and sequence. Glycans are also highly susceptible to dissociation by free radicals, mainly reactive oxygen species, which inspired our development of a free radical activated glycan sequencing (FRAGS) reagent, which combines a free radical precursor with a pyridine moiety that can be coupled to the reducing terminus of target glycans. Collisional activation of FRAGS-derivatized glycans generates a free radical that reacts to yield abundant cross-ring cleavages, glycosidic bond cleavages, and combinations of these types of cleavages with retention of charge at the reducing terminus. Branched sites are identified with the FRAGS reagent by the specific fragmentation patterns that are observed only at these locations. Mechanisms of dissociation as well as application of the reagents for both linear and highly branched glycan structure analysis are investigated and discussed. The approach developed here for glycan structure analysis offers unique advantages compared to earlier studies employing mass spectrometry for this purpose.

Original languageEnglish
Pages (from-to)10684-10692
Number of pages9
JournalJournal of the American Chemical Society
Volume135
Issue number29
DOIs
StatePublished - 24 Jul 2013

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Biomimetics
Free radicals
Free Radicals
Mass spectrometry
Polysaccharides
Mass Spectrometry
Acids
Protons
Pyridine
Chemical activation
Proton transfer
Catalysis
Enzymes
Oxygen
Chemical analysis
Gases

Cite this

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title = "Biomimetic reagents for the selective free radical and acid-base chemistry of glycans: Application to glycan structure determination by mass spectrometry",
abstract = "Nature excels at breaking down glycans into their components, typically via enzymatic acid-base catalysis to achieve selective cleavage of the glycosidic bond. Noting the importance of proton transfer in the active site of many of these enzymes, we describe a sequestered proton reagent for acid-catalyzed glycan sequencing (PRAGS) that derivatizes the reducing terminus of glycans with a pyridine moiety possessing moderate proton affinity. Gas-phase collisional activation of PRAGS-derivatized glycans predominately generates C1-O glycosidic bond cleavages retaining the charge on the reducing terminus. The resulting systematic PRAGS-directed deconstruction of the glycan can be analyzed to extract glycan composition and sequence. Glycans are also highly susceptible to dissociation by free radicals, mainly reactive oxygen species, which inspired our development of a free radical activated glycan sequencing (FRAGS) reagent, which combines a free radical precursor with a pyridine moiety that can be coupled to the reducing terminus of target glycans. Collisional activation of FRAGS-derivatized glycans generates a free radical that reacts to yield abundant cross-ring cleavages, glycosidic bond cleavages, and combinations of these types of cleavages with retention of charge at the reducing terminus. Branched sites are identified with the FRAGS reagent by the specific fragmentation patterns that are observed only at these locations. Mechanisms of dissociation as well as application of the reagents for both linear and highly branched glycan structure analysis are investigated and discussed. The approach developed here for glycan structure analysis offers unique advantages compared to earlier studies employing mass spectrometry for this purpose.",
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Biomimetic reagents for the selective free radical and acid-base chemistry of glycans : Application to glycan structure determination by mass spectrometry. / Gao, Jinshan; Thomas, Daniel A.; Sohn, Chang Ho; Beauchamp, J. L.

In: Journal of the American Chemical Society, Vol. 135, No. 29, 24.07.2013, p. 10684-10692.

Research output: Contribution to journalArticle

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