Protecting-Group-Controlled Enzymatic Glycosylation of Oligo-N-Acetyllactosamine Derivatives

Abstract

We describe a chemoenzymatic strategy that can give a library of differentially fucosylated and sialylated oligosaccharides starting from a single chemically synthesized tri-N-acetyllactosamine derivative. The common precursor could easily be converted into 6 different hexasaccharides in which the glucosamine moieties are either acetylated (GlcNAc) or modified as a free amine (GlcNH₂ ) or Boc (GlcNHBoc). Fucosylation of the resulting compounds by a recombinant fucosyl transferase resulted in only modification of the natural GlcNAc moieties, providing access to 6 selectively mono- and bis-fucosylated oligosaccharides. Conversion of the GlcNH₂ or GlcNHBoc moieties into the natural GlcNAc, followed by sialylation by sialyl transferases gave 12 differently fucosylated and sialylated compounds. The oligosaccharides were printed as a microarray that was probed by several glycan-binding proteins, demonstrating that complex patterns of fucosylation can modulate glycan recognition.

Keywords: glycan microarray; glycosyl transferases; glycosylation; lectin; regioselectivity.