Inhibition of glycoprotein processing by L-fructose and L-xylulose.
A number of unusual and rare carbohydrates were tested as potential inhibitors of various glycosidases, as well as inhibitors of N-linked oligosaccharide processing. The best inhibitors of several arylglycosidases and of glucosidase I were L-xylulose and L-fructose. Both of these sugars showed some inhibitory activity towards yeast alpha-glucosidase but were inactive against beta-glucosidase and other arylglycosidases. The inhibition of yeast alpha-glucosidase by L-xylulose was of a competitive nature and required a concentration of 1 x 10(-5) M for 50% inhibition. Both L-xylulose and L-fructose also inhibited the purified soybean glucosidase I, with 50% inhibition occurring at about 1 x 10(-4) M, but showed no inhibitory activity against soybean glucosidase II. When influenza virus-infected MDCK cells were raised in the presence of L-xylulose, there was a dose-dependent inhibition in the formation of complex types of oligosaccharides on the viral glycoproteins consistent with the inhibition of the processing glucosidase I. This inhibition resulted in the occurrence of oligosaccharides on the viral glycoproteins that were characterized as Glc3Man9(GlcNAc)2 structures. L-Fructose also inhibited glycoprotein processing in cell culture, and the inhibition resulted in the formation of similar oligosaccharides to those seen with L-xylulose. However, L-fructose was a poorer inhibitor than L-xylulose and required much higher concentrations for the same degree of inhibition. Neither of these compounds inhibited protein synthesis or the formation of lipid-linked saccharides in culture MDCK cells, even when tested at concentrations of 5 mg/ml (about 30 mM) of culture media.
Muniruzzaman
S
S
Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock 72205, USA.
Pan
Y T
YT
Zeng
Y
Y
Atkins
B
B
Izumori
K
K
Elbein
A D
AD
D000818:Animals; D002417:Cattle; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005632:Fructose / Q000494:pharmacology*; D006023:Glycoproteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors; D009975:Orthomyxoviridae / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D014764:Viral Proteins / Q000037:antagonists & inhibitors; D014996:Xylulose / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D006023:Glycoproteins; D014764:Viral Proteins; D005632:Fructose; D014996:Xylulose; D006026:Glycoside Hydrolases