Quantitative Analysis of Receptor Function of Ganglioside Lactone

神经节苷是动物细胞上的抗原、流感病毒的受体和细胞粘附分子。当处于温和的酸性条件下，神经节苷在唾液酸的羧基和邻近的糖的羟基之间形成一种内部酯，称为“内酯”。在肿瘤细胞和正常脑组织中均检测到神经节苷内酯。B16黑色素瘤免疫后建立的IgM单克隆抗体与GM3内酯的亲和力较GM3强。因此，神经节苷内酯被认为是B16黑色素瘤细胞的真正免疫原。在我们的研究中，GM3内酯与唾液酸结合蛋白（小麦胚芽凝集素，WGA）的结合亲和力比亲本GM3高。接下来，我们发现GM3内酯和GM4内酯具有与流感病毒血凝素结合而不被神经氨酸酶水解的潜力。流感病毒已知有膜蛋白，如血凝素和神经氨酸酶。血凝素选择性地与脂质偶联的唾液半乳糖基团结合。这些唾液糖脂也是神经氨酸酶的底物。探索未被神经氨酸酶水解的糖脂对于了解流感病毒转染宿主细胞的机制以及开发流感病毒抑制剂具有重要意义。

Gangliosides ate known as an antigen on animal cells, a receptor for influenza virus, and a cell adhesion molecule. When subjected to mild acidic condition, gangliosides form an internal ester, so called "lactone", between a carboxyl group of sialic acid and a hydroxyl group of neighboring saccharide. Ganglioside lactones have been detected in tumor cells and normal brain. An IgM monoclonal antibody established after immunization with B16 melanoma showed stronger affinity with GM3 lactone than with GM3. Therefore, ganglioside lactone is considered to be real immunogen on B16 melanoma cells.In our study, GM3 lactone showed higher binding affinity with a sialic acid-binding protein (wheat germ agglutinin, WGA) than the parent GM3 did. Next, we found that GM3 lactone and GM4 lactone has a potential to bind to influenza virus hemagglutinin without being hydrolyzed by neuraminidase. Influenza virus is known to have membrane proteins such as hemagglutinin and neuraminidase. Hemagglutinin selectively binds to sialylgalactose groups conjugated with lipids. Such the sialylglycolipids are also substrates for neuraminidase. Exploration of glycolipids that are not hydrolyzed by neuraminidase should be important to know the mechanisms for the transfection of influenza virus to host cells, and to develop inhibitors for influenza virus.