Studies on biological activities, their molecular mechanisms, and structure-function relationships of lectins from marine algae

海藻凝集素的生物活性、分子机制及构效关系研究

基本信息

批准号：
15380143
负责人：
HORI Kanji
金额：
$ 9.6万
依托单位：
Hiroshima University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

The studies were performed aimed at clarifying biological activities, their molecular mechanisms, and structure-function relationships of marine algal lectins, especially those that belong to a high-mannose N-glycan specific lectin family or a multifunctional low-molecular weight polypeptidic lectin family.With respect to a high-mannose N-glycan specific lectin family, first, the detailed carbohydrate-binding specificity and the primary structure of a red alga, Eucheuma serra lectin (ESA-2) were elucidated. Next, it was found that orally administration of ESA-2 suppressed the formation of colon aberrant crypt foci in mice received 1,2-dimethylhydrazine, due to the lower production of active oxygen in the colonic tissues. Relating to this, a receptor for ESA-2 on the cultured cells (HT-29) derived from human colonic cancer was identified using a newly established method for isolation of cell membrane receptors. In addition, the primary structure and the detailed carbohydrate-binding specificity of a cyanobacterium, Oscillatoria agardhii lectin (OAA), that belongs to this family, was elucidated. Furthermore, it was demonstrated that some lectins belonging to this family are very useful as affinity ligands for one-step purification of chicken monoclonal antibody that is usable for diagnosis of bovine spongiform encephalopathy (BSE).With respect to a multifunctional low-molecular weight polypeptidic lectin family, it was found that the lectin (hypnin A) from the red alga, Hypnea japonica is strictly specific for core α1-6 fucose in N-glycans, and would be useful as a reagent to detect cancer marker(s) as well as to prepare medicinal antibodies lacking the core α1-6 fucose that have effective antibody-dependent cellular cytotoxicity (ADCC)

The studies were performed aimed at clarifying biologic activities, their molecular mechanisms, and structure-function relationships of marine algal lectures, especially those that belong to a high-mannose N-glycan specific lecture family or a multifunctional low-molecular weight polypeptidic lecture family.With respect to a high-mannose N-glycan specific lecture family, first, the detailed carbonhydrate-binding specificity and the primary structure阐明了红色藻类苏拉（Eucheuma Serra）演讲（ESA-2）的仪式。接下来，发现口服ESA-2抑制了小鼠的结肠异常crypt焦点的形成，这是由于结肠组织中活性氧的产生较低，因此接受了1,2-二甲基氢嗪。与此相关的是，使用新建立的细胞膜受体分离的方法鉴定了培养细胞上ESA-2的受体（HT-29）（HT-29）。此外，阐明了属于该家族的蓝细菌，振荡器振荡器（OAA）的主要结构和详细的碳水化合物结合特异性（OAA）。此外，已经证明，属于该家族的一些讲座非常有用，作为亲和力配体用于一步纯化鸡肉单克隆抗体的亲和力，可用于诊断牛为牛发起的脑病诊断（BSE）。 Japonica严格特异性对于N-Glycans中的Coreα1-6fucose，可作为检测癌症标志物的试剂以及制备缺乏有效抗体依赖性抗体依赖性细胞毒性（ADCC）的癌症α1-6富糖的医学抗体的试剂。