Glycan Imaging Mass Spectrometry

Blaschke, Calvin R.K.; McDowell, Colin; Black, Alyson; Mehta, Anand; Angel, Peggi; Drake, Richard

doi:10.1016/j.cll.2021.03.005

Cited by 20 publications

(10 citation statements)

References 118 publications

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“…In the present study, we have developed a multifunctional isomer-targeted sialic acid derivatization strategy compatible with clinical tissues, biofluids, and cultured cells. The AAXL and AAN 3 approach synergizes the established workflows for amidation of the lactone intermediate in α-2,3-linked sialic acids, , bioorthogonal sugar azides and alkynes, and N -glycan imaging mass spectrometry ,, resulting in new tools with unique features. First, it can be used to specifically introduce bioorthogonal groups into α2,3 and α2,8 sialic acids attached to proteins and likely lipids but not α2,6 sialic acids and other carboxylate-containing moieties.…”

Section: Discussionmentioning

confidence: 99%

“…In 2016, a chemical amidation reaction workflow was reported for application to sialic acid linkage-specific derivatization directly in formalin-fixed paraffin-embedded tissues for N -glycan matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS) analysis . Different N -glycan IMS workflows have evolved over the past decade, − and stabilizing sialic acids to differentiate α2,3 from α2,6-sialylated N -glycan isomers for spatial profiling in tissues is very effective. ,, The goal of the current study was to modify the original amidation–amidation (AA) workflow to generate bioorthogonal variants of α2,3 and α2,8 sialic acids in biological systems. This was accomplished by using alkyne-amine and azide-amine compounds as the second amidation reactants, i.e., the primary amine reagents that open the lactone intermediate.…”

Section: Introductionmentioning

confidence: 99%

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Bioorthogonal Chemical Labeling Probes Targeting Sialic Acid Isomers for N-Glycan MALDI Imaging Mass Spectrometry of Tissues, Cells, and Biofluids

McDowell

Blaschke

et al. 2023

Anal. Chem.

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Sialic acid isomers attached in either α2,3 or α2,6 linkage to glycan termini confer distinct chemical, biological, and pathological properties, but they cannot be distinguished by mass differences in traditional mass spectrometry experiments. Multiple derivatization strategies have been developed to stabilize and facilitate the analysis of sialic acid isomers and their glycoconjugate carriers by high-performance liquid chromatography, capillary electrophoresis, and mass spectrometry workflows. Herein, a set of novel derivatization schemes are described that result in the introduction of bioorthogonal click chemistry alkyne or azide groups into α2,3and α2,8-linked sialic acids. These chemical modifications were validated and structurally characterized using model isomeric sialic acid conjugates and model protein carriers. Use of an alkyne-amine, propargylamine, as the second amidation reagent effectively introduces an alkyne functional group into α2,3-linked sialic acid glycoproteins. In tissues, serum, and cultured cells, this allows for the detection and visualization of Nlinked glycan sialic acid isomers by imaging mass spectrometry approaches. Formalin-fixed paraffinembedded prostate cancer tissues and pancreatic cancer cell lines were used to characterize the numbers and distribution of alkyne-modified α2,3-linked sialic acid N-glycans. An azide-amine compound with a poly(ethylene glycol) linker was evaluated for use in histochemical staining. Formalin-fixed pancreatic cancer tissues were amidated with the azide amine, reacted with biotin-alkyne and copper catalyst, and sialic acid isomers detected by streptavidin-peroxidase staining. The direct chemical introduction of bioorthogonal click chemistry reagents into sialic acid-containing glycans and glycoproteins provides a new glycomic tool set to expand approaches for their detection, labeling, visualization, and enrichment.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Bioorthogonal Chemical Labeling Probes Targeting Sialic Acid Isomers for N-Glycan MALDI Imaging Mass Spectrometry of Tissues, Cells, and Biofluids

McDowell

Blaschke

et al. 2023

Anal. Chem.

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“…It does, however, imply that our review does not constitute a fully comprehensive overview of the whole field of MSI. We hence want to refer the reader to the many reviews that focus on and cover specific aspects of the large field of MSI, such as unsupervised data analysis 13 or the imaging of glycans 154 and other molecular classes.…”

Section: Discussionmentioning

confidence: 99%

State-of-the-art mass spectrometry imaging applications in biomedical research

Krestensen,

Heeren,

Balluff

2023

Analyst

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“…Ongoing advances in MSI in sample preparation, ion sources, and mass analyzers have enabled broader and more diverse research in glycoscience. As these have been reviewed recently, − we focus on a special topic: mass-tag-based strategies for MSI of glycans. A typical probe contains a labeling module targeting known GOIs and a mass tag (or several mass tags) that can be easily released for MALDI detection.…”

Section: Recent Progress In Glycan Imagingmentioning

confidence: 99%

In Situ Glycan Analysis and Editing in Living Systems

Li,

Wang,

Chen

et al. 2024

JACS Au

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Besides proteins and nucleic acids, carbohydrates are also ubiquitous building blocks of living systems. Approximately 70% of mammalian proteins are glycosylated. Glycans not only provide structural support for living systems but also act as crucial regulators of cellular functions. As a result, they are considered essential pieces of the life science puzzle. However, research on glycans has lagged far behind that on proteins and nucleic acids. The main reason is that glycans are not direct products of gene coding, and their synthesis is nontemplated. In addition, the diversity of monosaccharide species and their linkage patterns contribute to the complexity of the glycan structures, which is the molecular basis for their diverse functions. Research in glycobiology is extremely challenging, especially for the in situ elucidation of glycan structures and functions. There is an urgent need to develop highly specific glycan labeling tools and imaging methods and devise glycan editing strategies. This Perspective focuses on the challenges of in situ analysis of glycans in living systems at three spatial levels (i.e., cell, tissue, and in vivo) and highlights recent advances and directions in glycan labeling, imaging, and editing tools. We believe that examining the current development landscape and the existing bottlenecks can drive the evolution of in situ glycan analysis and intervention strategies and provide glycan-based insights for clinical diagnosis and therapeutics.

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Glycan Imaging Mass Spectrometry

Cited by 20 publications

References 118 publications

Bioorthogonal Chemical Labeling Probes Targeting Sialic Acid Isomers for N-Glycan MALDI Imaging Mass Spectrometry of Tissues, Cells, and Biofluids

Bioorthogonal Chemical Labeling Probes Targeting Sialic Acid Isomers for N-Glycan MALDI Imaging Mass Spectrometry of Tissues, Cells, and Biofluids

State-of-the-art mass spectrometry imaging applications in biomedical research

In Situ Glycan Analysis and Editing in Living Systems

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