Inhibition of glycoprotein processing by L-fructose and L-xylulose
Inhibition of glycoprotein processing by L-fructose and L-xylulose
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DOI：
10.1093/glycob/6.8.795
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发表时间：
1996-12-01
期刊：
影响因子：
4.3
通讯作者：
Elbein, AD
中科院分区：
文献类型：
--
作者：
Muniruzzaman, S;Pan, YT;Elbein, AD
一些罕见的碳水化合物是各种糖苷酶的潜在抑制剂，也是N-连接寡糖加工的抑制剂，对几种芳基糖苷酶和葡萄糖苷酶I的最佳抑制剂是L-木果糖和L-果糖，这两种糖对酵母α-葡萄糖苷酶有一定的抑制活性，但对β-葡萄糖苷酶和其他芳基糖苷酶没有活性。L-木糖对酵母α-葡萄糖苷酶的抑制是竞争性的，需要1×10(-5)M的浓度才能抑制50%。L-木果糖和L-果糖对纯化的大豆糖苷酶I也有抑制作用。在约1×10(-4)M处有50%的抑制作用，但对大豆葡萄糖苷酶II无抑制活性。当流感病毒感染的MDCK细胞在L木糖的存在下培养时，对病毒糖蛋白形成复合型寡糖的抑制与对葡萄糖苷酶I的抑制一致，这种抑制作用导致病毒糖蛋白上出现寡糖，其特征是Glc(3)Man(9)(GIcNAc)(2)结构，L果糖也抑制细胞培养中糖蛋白的加工。这种抑制作用与L-木糖类似，但L-果糖的抑制作用比L-木糖差，需要更高的浓度才能达到同样的抑制程度，即使在5 mg/ml(约30 mM)的培养液中，这两种化合物也不能抑制培养的mDCK细胞蛋白质合成或脂键糖的形成。
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-xyIulose 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 Glc(3)Man(9)(GIcNAc)(2) structures, L-Fructose also inhibited glycoprotein processing in cell culture, and that 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 cultured MDCK cells, even when tested at concentrations of 5 mg/ml (about 30 mM) of culture media.