Abstract

Gangliosides are a family of conjugates consisting of a polar sialoglycan head group and a hydrophobic ceramide tail. Gangliosides are of high abundance in neuronal tissues and are involved in numerous biological processes, such as cell-cell recognition, adhesion, and signal transduction. Alteration of the ganglioside profile is associated with various neurodegenerative diseases and there is indication that gangliosides are involved in the pathogenesis of Parkinson’s and Huntington’s disease. The development of refined methods for the analysis of gangliosides by high-performance liquid chromatography coupled to mass spectrometry (HPLC-MS) has supported research with qualitative and quantitative data. However, the amphiphilic character of gangliosides renders their separation and mass spectrometric analysis challenging. In this article, the strengths of hydrophilic interaction liquid chromatography (HILIC) for baseline separation of gangliosides, including two structural isomers, and their structural characterization by tandem mass spectrometry are demonstrated. The importance of ion source parameter optimization is highlighted to prevent misleading ganglioside transformation due to in-source dissociation.

Highlights

  • Gangliosides are a family of conjugates consisting of a polar sialoglycan head group and a hydrophobic ceramide tail

  • Wilkins at the University of California, Riverside, he became leader of the mass spectrometry facility at the Department of Chemistry, Biochemistry and Pharmaceutical Sciences of the University of Bern, where he was appointed Associate Professor in 2017. Research of this group focuses on the characterization of biomolecule structures by mass spectrometry and on the elucidation of the processes involved in the dissociation of ions in the gas-phase

  • hydrophilic interaction liquid chromatography (HILIC) demonstrated its excellent capability in separating gangliosides based on their hydrophilic head group, while putting aside the difference in hydrophobicity originating from different ceramide compositions

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Summary

Introduction

Gangliosides are a family of conjugates consisting of a polar sialoglycan head group and a hydrophobic ceramide tail. Research of this group focuses on the characterization of biomolecule structures by mass spectrometry and on the elucidation of the processes involved in the dissociation of ions in the gas-phase. GD1a and GD1b originate from the biosynthetic a and b series, respectively, and both gangliosides comprise two sialic acid moieties along with four uncharged carbohydrates.

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