Preparation and application of a ‘clickable’ acceptor for enzymatic synthesis of heparin oligosaccharides

A ‘clickable’ disaccharide was prepared by treating the aldehyde precursor with hydroxylamine, followed by the catalytic hydrogenation and diazotransfer reaction. This disaccharide was successfully applied to the elongation of the backbone construction of ultralow molecular weight (ULMW) heparins using two bacterial glycosyl transferases, N-acetyl glucosaminyl transferase from Escherichia coli K5 (KfiA) and heparosan synthase-2 (pmHS2) from Pasteurella multocida.

Graphical abstractTetrasaccharide as an acceptor with an ‘clickable’ azido group.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► A disaccharide was prepared by chemical treatment of heparosan. ► An azido group was introduced into this heparosan disaccharide. ► The azido heparosan disaccharide was used as a glycosylation acceptor. ► A heparin tetrasaccharide was enzymatically synthesized.