The cell surface of all vertebrate organisms is covered with a thick layer of glycosylated molecules, collectively termed as the cell's glycome. Changes in the glycome reflect the changes in the cell's developmental stages and changes taking place during its transformation of state. In the past three years, my laboratory has developed a supersensitive and biocompatible reaction, the ligand-assisted Cu-catalyzed azide-alkyne cycloaddition. This reaction, when combined with either a metabolic or an in situ chemoenzymatic strategy, has permitted the incorporation of small-molecule fluorescent probes onto cell-surface glycans directly for their visualization in living systems. In live mammalian cells, we discovered that activated lymphocytes display different glycosylation patterns compared to na�ve cells.  In zebrafish embryos, the labeled fucosylated glycans could be detected at as early as the two-cell stage on the enveloping layer of the embryos. However, only weak labeling was observed in internal organs during the first three days post fertilization with a burst of fucosylation observed on day four.  This observation correlates with the dynamic expression of GDP-fucose transporters during zebrafish early embryogenesis.  Overexpression of the GDP-fucose transporter, slc35C1, caused a dorsalized phenotype in zebrafish embryos due to protein hyperfucosylation. Using a combination of biochemical and genetic tools, we discovered the underline mechanism linking fucosylation to wnt signaling and embryonic patterning.

Chemical tools for deciphering the in vivo functions of glycans

247th National Meeting (2014)

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