Inhibition of L-Fucokinase from Rat Liver by L-Fucose Analogues In Vitro

Abstract

By investigating the effects of more than 15 different L-fucose analogues on the activity of L-fucokinase (EC 2.7.1.52) from rat liver in vitro, certain structural requirements for potent inhibition of this enzyme were established. Of the novel compounds, 4,6-dideoxy-L-xylo-hexopyranose (4) and methyl 4,6-dideoxy-4-iodo-L-glucopyranose (9) were found to be competitive inhibitors with K_i-values of 0.5 mM and 5.0 mM respectively. Thus 4,6-dideoxy-L-xylo-hexopyranose is a better inhibitor of L-fucokinase than methyl-α-L-fucoside (1). Uptake of L-fucose into rat hepatoma cells is reduced by 52% in the presence of the deoxy derivative (4), leading to a decrease of 45% in the incorporation of L-fucose into total cellular glycoproteins.

Key Words: :

• Rat liver
• L-fucokinase
• L-fucose analogues
• Inhibition
• glycosylation.
• Fuc-1-P
• β-fucosyl-1-phosphate
• GDP-L-Fuc
• guanosinediphospho-L-fucose.