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Updated: Jun 5, 2026

Metabolic Glycoengineering of Sialic Acid Using N-acyl-modified Mannosamines
Published on: November 25, 2017
Calystegine B3 as a specific inhibitor for cytoplasmic alpha-mannosidase, Man2C1
Atsushi Kato1, Li Wang, Kumiko Ishii
1Department of Hospital Pharmacy, University of Toyama, Toyama 930-0194, Japan.
Abstract:
Cytoplasmic α-mannosidase (Man2C1) has been implicated in non-lysosomal catabolism of free oligosaccharides derived from N-linked glycans accumulated in the cytosol. Suppression of Man2C1 expression reportedly induces apoptosis in various cell lines, but its molecular mechanism remains unclear. Development of a specific inhibitor for Man2C1 is critical to understanding its biological significance. In this study, we identified a plant-derived alkaloid, calystegine B(3), as a potent specific inhibitor for Man2C1 activity. Biochemical enzyme assay revealed that calystegine B(3) was a highly specific inhibitor for Man2C1 among various α-mannosidases prepared from rat liver. Consistent with this in vitro result, an in vivo experiment also showed that treatment of mammalian-derived cultured cells with this compound resulted in drastic change in both structure and quantity of free oligosaccharides in the cytosol, whereas no apparent change was seen in cell-surface oligosaccharides. Calystegine B(3) could thus serve as a potent tool for the development of a highly specific in vivo inhibitor for Man2C1.
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