Fucosyltransferase-specific inhibition via next generation of fucose mimetics

Abstract

The ability to custom-modify cell surface glycans holds great promise for treatment of a variety of diseases. We propose a glycomimetic of L-fucose that markedly inhibits the creation of sLe^X by FTVI and FTVII, but has no effect on creation of Le^X by FTIX. Our findings thus indicate that selective suppression of sLex display can be achieved, and STD-NMR studies surprisingly reveal that the mimetic does not compete with GDP-fucose at the enzymatic binding site.