Fragmentation of Oligosaccharides: Mechanistic Insights for Glycomics

Alterations in sugar structure are associated with diseases, and clinical glycomics is emerging as a tool for their diagnostics. This is most commonly achieved using a controlled collision-induced dissociation (CID) of larger oligosaccharides into fragments and measuring their mass in a mass spectrometer. Due to the complexity of sugars, and particularly their unusual fragmentation mechanisms, the underlying processes are poorly understood. Making glycan fragmentation predictable is highly desirable and would transform glycomics from an expert technique into a widely applicable tool that can be used by non-specialists. Here, we review the current understanding of glycan fragmentation mechanisms in CID, with a particular emphasis on hexose migrations and the anomeric memory. We discuss challenges and perspectives for future investigations, opening the window to a widespread use of glycomics in clinical applications based on a fundamental understanding of glycan fragmentation.