Identifying effective strategies to manage and treat multiple sclerosis (MS) is of central importance. As a neurodegenerative disease, MS is characterized by an auto-immunogenic demyelination of the central nervous system. This process removes the insulating bio-membrane, comprised of oligodendrocytes which sheath several axons. A feature of these glial cells is a high concentration of gangliosides on their surface, one of which sialosylgalactosylceramide ganglioside (GM4). GM4, a simple disaccharide, is conspicuously abundant in oligodendrocytes and exhibits a high affinity towards myelin basic protein (MBP). This renders GM4 a potential tool for imaging or stimulating the differentiation process of oligodendrocyte precursor cells (OPC). To achieve increased stability, a single site OH → F substitution was applied in the GM4 epitope, making the glycosidic bond less prone to enzymatic hydrolysis. The 2-deoxy-2-fluoro motif is also highly desirable for its similarity to the common PET-tracer 18-FDG, indicating its potential use as an imaging agent. Additionally, the implementation of fluorine in the C2-position of carbohydrates increases β-selectivity during glycosylation step which is advantageous in oligosaccharide synthesis. Herein we present the syntheses of the GM4 pseudo-wildtype epitope (1), its fluorinated analogue (2) and explore their influence in OPC differentiation.

Fluorinated analogue of the ganglioside GM4 and its application in oligodendrocyte upregulation

256th National Meeting (2018)

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