INHIBITION OF GLYCOPROTEIN PROCESSING BY L-FRUCTOSE AND L-XYLULOSE

A number of unusual and rare carbohydrates were tested as potential in hibitors of various glycosidases, as well as inhibitors of N-linked ol igosaccharide processing, The best inhibitors of several arylglycosida ses and of glucosidase I were L-xylulose and L-fructose, Both of these sugars showed some inhibitory activity towards yeast alpha-glucosidas e but were inactive against beta-glucosidase and other arylglycosidase s, The inhibition of yeast alpha-glucosidase by L-xyIulose was of a co mpetitive 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 I I, When influenza virus-infected MDCK cells were raised in the presenc e of L-xylulose, there was a dose-dependent inhibition in the formatio n of complex types of oligosaccharides on the viral glycoproteins cons istent with the inhibition of the processing glucosidase I, This inhib ition resulted in the occurrence of oligosaccharides on the viral glyc oproteins that were characterized as Glc(3)Man(9)(GIcNAc)(2) structure s, L-Fructose also inhibited glycoprotein processing in cell culture, and that inhibition resulted in the formation of similar oligosacchari des to those seen with L-xylulose, However, L-fructose was a poorer in hibitor than L-xylulose and required much higher concentrations for th e same degree of inhibition, Neither of these compounds inhibited prot ein synthesis or the formation of lipid-linked saccharides in cultured MDCK cells, even when tested at concentrations of 5 mg/ml (about 30 m M) of culture media.