INHIBITION OF L-FUCOKINASE FROM RAT-LIVER BY L-FUCOSE ANALOGS IN-VITRO

By investigating the effects of more than 15 different L-fucose analog ues on the activity of L-fucokinase (EC 2.7.1.52) from rat liver in vi tro, certain structural requirements for potent inhibition of this enz yme were established. Of the novel compounds, 4,6-dideoxy-L-xylo-hexop yranose (4) and methyl 4,6-dideoxy-4-iodo-L-glucopyranose (9) were fou nd to be competitive inhibitors with K-i-values of 0.5 mM and 5.0 mM r espectively. Thus 4,6-dideoxy-L-xylo-hexopyranose is a better inhibito r of L-fucokinase than methyl-alpha-L-fucoside (1). Uptake of L-fucose into rat hepatoma cells is reduced by 52% in the presence of the deox y derivative (4), leading to a decrease of 45% in the incorporation of L-fucose into total cellular glycoproteins.