Custom-site Modification of Cell Surface Fucosylation via Next Generation Fucosyltransferase Inhibitors.
Fucosyltransferase-specific inhibition via next generation of fucose mimetics
Kyle C. Martin, Jacopo Tricomi, Francisco Corzana, Ana García-García, Laura Ceballos-Laita, Thomas Hicks, Serena Monaco, Jesus Angulo, Ramon Hurtado-Guerrero, Barbara Richichi and Robert Sackstein. Chemical Communications. 2021.
DOI: 10.1039/D0CC04847J
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 sLeX by FTVI and FTVII, but has no effect on creation of LeX 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.
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 sLeX by FTVI and FTVII, but has no effect on creation of LeX 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.