Metabolic glycoengineering in hippocampal neurons: cellular uptake of exogenously supplied non-natural sugars

Glycans are involved in a plethora of important physiological processes in both the developing and the adult nervous system: cell migration, neurite outgrowth and fasciculation, synapse formation, and modulation of synaptic efficacy are all related with glycan expression and bioactivity [1]. Targeting elucidation of the glycan role(s) during neurite outgrowth, we synthesised peracetylated azido-functionalized analogues of three natural sugars, namely mannose, glucose and fucose [2]. These unnatural sugars were supplied exogenously to hippocampal neuronal primary cell cultures and the metabolic pathways involved in the glycosylation process were exploited. Specifically, we investigated the influence of the chemical modification on the uptake and biosynthetic pathways of the sugars in vitro. Furthermore, we studied the spatial and temporal distribution of glycans at the cell surface by tracking the modified sugars using click chemistry with labeled cyclooctyne probes.

[1] R Kleene, M Schachner, Nature Reviews - Neuroscience 5, 195 (2004)
[2] E Saxon, CR Bertozzi, Science 287, 2007 (2000)

The authors would like to acknowledge the EU project POLARIS (REGPOT-CT2012–316331)