Chemoenzymatic Synthesis of Sialyl Sulfo-Oligosaccharides as Potent Siglec-8 Ligands via Transglycosylation Catalyzed by Keratanase II.

Sialyl type-II sulfo-oligosaccharides are gaining much attention as bioactive ligands for Siglecs. In this study, we have achieved the first synthesis of sialyl type-II sulfo-oligosaccharides chemoenzymatically by utilizing the transglycosylation activity of keratanase II. The oxazoline derivative of α(2→3)-sialylated 6,6'-di-sulfo-LacNAc ( 3 ) was newly designed as the glycosyl donor for enzymatic transglycosylation. Keratanase II efficiently catalyzed the transglycosylation of 3 with two kinds of glycosyl acceptors, 6-sulfo-Lewis X and 6,6'-di-sulfo-LacNAc derivatives, providing sialyl sulfo-hexasaccharide ( 1 ) and sialyl sulfo-pentasaccharide ( 2 ) with 86 and 95% yields, respectively. The products 1 and 2 showed higher affinity to Siglec-8 with K D 70 and 25 μmol·L -1 , respectively, compared to the known ligand of the α(2→3)-sialylated 6,6'-di-sulfo-Lewis X with K D 185 μmol·L -1 . Thus, this study will advance not only the study of Siglec-8 biology but also the exploration of functions of sialyl sulfo-oligosaccharides having various microstructures.