Design and Synthesis of Peptide Mimetics of GDP-Fucose: Targeting Inhibitors of Fucosyltransferases

Abstract Novel peptide mimetics of GDP-fucose were designed and synthesized targeting inhibitors of the fucosyltransferases that transfer L-fucose from GDP-fucose to oligosaccharides, on the basis of the background that nikkomycin Z, a peptide mimetic of UDP-N-acetylglucosamine, shows potent inhibitory activity toward an N-acetylglucosamine transfer enzyme. The synthetic routes of the GDP-fucose mimetics take advantage of an enzymatic aldol reaction catalyzed by L-threonine aldolase to prepare the guanine carrying β-hydroxy-α-L-amino acid, a key synthetic intermediate.