Mehta A, Zitzmann N, Rudd P M, Block T M, Dwek R A
The Glycobiology Institute, Department of Biochemistry, Oxford University, UK.
FEBS Lett. 1998 Jun 23;430(1-2):17-22. doi: 10.1016/s0014-5793(98)00525-0.
N-Linked oligosaccharides play many roles in the fate and functions of glycoproteins. One function is to assist in the folding of proteins by mediating interactions of the lectin-like chaperone proteins calnexin and calreticulin with nascent glycoproteins. These interactions can be prevented by inhibitors of the alpha-glucosidases and this causes some proteins to be misfolded and retained within the endoplasmic reticulum. In human immunodeficiency virus (HIV) and hepatitis B virus (HBV) the misfolding of key viral envelope glycoproteins interferes with the viral life cycle. It has been demonstrated in an animal model of chronic HBV that glucosidase inhibitors can alter glycosylation and have anti-viral activity. As the mechanism of action of alpha-glucosidase inhibitors is the induction of misfolded or otherwise defective viral glycoproteins, such inhibitors may be useful therapeutics for many viruses, especially those which bud from the endoplasmic reticulum (where protein folding takes place). For example bovine viral diarrhea virus, a pestivirus akin to hepatitis C virus, is also extremely sensitive to glucosidase inhibition.
N-连接寡糖在糖蛋白的命运和功能中发挥着多种作用。其中一个功能是通过介导凝集素样伴侣蛋白钙连蛋白和钙网蛋白与新生糖蛋白的相互作用来协助蛋白质折叠。α-葡萄糖苷酶抑制剂可阻止这些相互作用，这会导致一些蛋白质错误折叠并滞留在内质网内。在人类免疫缺陷病毒（HIV）和乙型肝炎病毒（HBV）中，关键病毒包膜糖蛋白的错误折叠会干扰病毒生命周期。在慢性HBV动物模型中已证明，葡萄糖苷酶抑制剂可改变糖基化并具有抗病毒活性。由于α-葡萄糖苷酶抑制剂的作用机制是诱导错误折叠或有其他缺陷的病毒糖蛋白，此类抑制剂可能是许多病毒的有用治疗药物，尤其是那些从内质网（蛋白质折叠发生的地方）出芽的病毒。例如，牛病毒性腹泻病毒，一种与丙型肝炎病毒类似的瘟病毒，对葡萄糖苷酶抑制也极为敏感。
