To probe the utility of a multivalent approach for fucosidase inhibition, a series of di- and tri-valent imino sugars based on L-fuco-configured 1,4-imino- and 1,4-bis(imino)-cyclitol epitopes has been synthesized and analyzed for fucosidase inhibition with the best trivalent species yielding a modest improvement in binding constant. Structural analysis of a representative pair of mono- and tri-valent imino sugars has been performed on a bacterial fucosidase, BtFuc2970. The 3D structures show binding of the imino-cyclitol in the 3E conformation, consistent with the known pathway for fucosidase action. Di- and tri-valent imino sugars based on L-fuco-configured 1,4-imino- and 1,4-bis(imino)-cyclitol moieties present α-L-fucosidase inhibitory activities in the μM and nM range.
- Imino sugars
- Structure-activity relationships