Isolation and analysis of mode of action of novel inhibitors of intracellular translocation of glycoproteins

需要新的抑制剂来分析糖蛋白在细胞内转运的机制。为此，设计了一种新的筛选方法。该方法是一种简便而有效的分离特异性抑制剂的方法。这种方法的策略是基于这样的假设，即这些抑制剂应该在不影响糖蛋白合成的情况下抑制被包膜病毒感染后的细胞融合。从土壤样品中分离的微生物培养物中寻找了抑制剂，并进行了分离。这些抑制剂的特性有待进一步研究，但这些抑制剂不同于那些已知的抑制糖蛋白细胞内转位的药物。在这些抑制剂的存在下，水泡性口炎病毒G蛋白在细胞内积聚，且相对分子质量小于对照成熟G蛋白。这种分子量的下降是由于糖侧链的加工不完整造成的，这表明它的细胞内转位在到达高尔基体的转运室之前就停止了。他们的行动模式目前正在调查中。

Novel inhibitors are desired to analyze the mechanism of intracellular translocation of glycoproteins. For this purpose, a new screening method has been devised. This method is convenient but efficient to isolate specific inhibitors. The strategy of this method is based on the assumption that such inhibitors should inhibit cell fusion after infection with enveloped viruses without affecting glycoprotein synthesis. Inhibitors have been searched among cultures of microbes isolated from soil samples, and isolated. Characterization of these inhibitors waits for further investigation, but these inhibitors are different from those known to inhibit intracellular translocation of glycoproteins. In the presence of these inhibitors, vesicular stomatitis virus G protein accumulates intracellularly and has a molecular weight smaller than that of control mature G protein. This decrease in molecular weight is caused by incompleteness of processing of the saccharide side chain indicating that its intracellular translocation is stopped before reaching the trans compartment of the Golgi apparatus. Their mode of action is now under investigation.