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

  • Biomacromolecules. 2022 Jan 10;23(1):316-325. doi: 10.1021/acs.biomac.1c01289.
Shiori Yuge  1 ,  Ayaka Tateishi  1 ,  Keiji Numata  1 ,  Masashi Ohmae  1
Affiliations
  • 1. Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 615-8510, Japan.
PMID: 34914356 DOI: 10.1021/acs.biomac.1c01289
Abstract

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 KD 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 KD 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.

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