Diversity-Oriented Chemoenzymatic Synthesis of Sulfated and Nonsulfated Core 2 O-GalNAc Glycans

A diversity-oriented chemoenzymatic approach for the collective preparation of sulfated core 2 O-GalNAc glycans and their nonsulfated counterparts was described. A sulfated trisaccharide and a nonsulfated trisaccharide were chemically synthesized by combining flexible protected group manipulations and sequential one-pot glycosylations. The divergent enzymatic extension of these two trisaccharides, using a panel of robust glycosyltransferases that can recognize sulfated substrates and differentiating the branches with specifically designed glycosylation sequences to achieve regioselective sialylation, provided 36 structurally well-defined O-GalNAc glycans.

Automated summary

A diversity-oriented chemoenzymatic approach was used for the collective preparation of sulfated core 2 O-GalNAc glycans and their nonsulfated counterparts. A sulfated trisaccharide and a nonsulfated trisaccharide were chemically synthesized, then enzymatic extension was carried out using a panel of robust glycosyltransferases to achieve regioselective sialylation, resulting in the generation of 36 structurally well-defined O-GalNAc glycans.