Search

Melibiosamine (Gal-α(1,6)-GlcNH 2 ), consisting of galactose and glucosamine linked by an α(1,6)-glycosidic bond, is an artificial disaccharide derivative that selectively inhibits the proliferation of K562 tumor cells relative to HUC-F2 normal cells. In this study, we employed a linkage-editing strategy to synthesize CH 2 - and CHF-linked melibiosamine analogs through chemo- and stereoselective hydrogenation of fluorovinyl- C -glycoside. ( R )-CHF-Melibiosamine exhibited more potent antiproliferative activity than O -linked melibiosamine, while ( S )-CHF-melibiosamine was less potent.

The acetal ( O -glycoside) bonds of glycans and glycoconjugates are chemically and biologically vulnerable, and therefore C -glycosides are of interest as more stable analogs. We hypothesized that, if the O -glycoside linkage plays a vital role in glycan function, the biological activities of C -glycoside analogs would vary depending on their substituents. Based on this idea, we adopted a "linkage-editing strategy" for the creation of glycan analogs (pseudo-glycans). We designed three types of pseudo-glycans with CH 2 and CHF linkages, which resemble the O -glycoside linkage in terms of bond lengths, angles, and bulkiness, and synthesized them efficiently by means of fluorovinyl C -glycosylation and selective hydrogenation reactions. Application of this strategy to isomaltose (IM), an inducer of amylase expression, and α-GalCer, which activates iNKT cells, resulted in the discovery of CH 2 -IM, which shows increased amylase production ability, and CHF-α-GalCer, which shows activity opposite that of native α-GalCer, serving as an antagonist of iNKT cells.