Total Chemical Syntheses of the GM 3 and F-GM 3 Ganglioside Epitopes and Comparative Pre-Clinical Evaluation for Non-Invasive Imaging of Oligodendrocyte Differentiation.

Gangliosides are intimately involved in a plenum of (neuro)inflammatory processes, yet progress in establishing structure-function interplay is frequently hindered by the availability of well-defined glycostructures. Motivated by the ubiquity of the ganglioside GM in chemical neurology, and in particular by its conspicuous presence in myelin, a chemical synthesis of the GM epitope was developed with a view to pre-clinical validation as a tracer. The suitability of this scaffold for the non-invasive imaging of oligodendrocyte differentiation in Multiple Sclerosis is disclosed. The stereocontrolled synthesis of a site-selectively fluorinated analog (F-GM) is also disclosed to enable a comparative analysis in oligodendrocyte (OL) differentia-tion. Whereas the native epitope caused a decrease in viability in a dose dependent manner, addition of distinct F-GM concen-trations over 48 h had no impact on OL viability. This is likely a consequence of the enhanced hydrolytic stability imparted by fluorination and highlights the potential of fluorinated glycostructures in the field of molecular imaging. Given the predominant expression of GM in oligodendrocytes and its capacity to interact with myelin associated proteins, this pre-clinical evaluation has revealed F-GM to be an intriguing candidate for neurological imaging.