Mammalian galectins bind Galactoseβ1–4Fucose disaccharide, a unique structural component of protostomial N-type glycoproteins

Abstract

Galactoseβ1–4Fucose (Galβ1–4Fuc) is a unique disaccharide exclusively found in N-glycans of protostomia, and is recognized by some galectins of Caenorhabditis elegans and Coprinopsis cinerea. In the present study, we investigated whether mammalian galectins also bind such a disaccharide. We examined sugar-binding ability of human galectin-1 (hGal-1) and found that hGal-1 preferentially binds Galβ1–4Fuc compared to Galβ1–4GlcNAc, which is its endogenous recognition unit. We also tested other human and mouse galectins, i.e., hGal-3, and -9 and mGal-1, 2, 3, 4, 8, and 9. All of them also showed substantial affinity to Galβ1–4Fuc disaccharide. Further, we assessed the inhibitory effect of Galβ1–4Fuc, Galβ1–4Glc, and Gal on the interaction between hGal-1 and its model ligand glycan, and found that Galβ1–4Fuc is the most effective. Although the biological significance of galectin−Galβ1–4Fuc interaction is obscure, it might be possible that Galβ1–4Fuc disaccharide is recognized as a non-self-glycan antigen. Furthermore, Galβ1–4Fuc could be a promising seed compound for the synthesis of novel galectin inhibitors.