title: 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 Ki-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-alpha-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.
authors.affiliation: Institut für Molekularbiologie und Biochemie der Freien Universität Berlin, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Zeitler
authors.forename: S
authors.initials: S
authors.lastname: Danneschewski
authors.forename: T
authors.initials: T
authors.lastname: Lindhorst
authors.forename: J
authors.initials: J
authors.lastname: Thiem
authors.forename: W
authors.initials: W
authors.lastname: Reutter
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005643:Fucose / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006154:Guanosine Diphosphate Fucose / Q000096:biosynthesis; D008099:Liver / Q000201:enzymology*; D008114:Liver Neoplasms, Experimental; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors*; D051381:Rats; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D004791:Enzyme Inhibitors; D006154:Guanosine Diphosphate Fucose; D005643:Fucose; D017853:Phosphotransferases (Alcohol Group Acceptor); C020153:fucokinase