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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)

本研究旨在阐明海藻凝集素的生物学活性、分子机制和结构-功能关系，特别是高甘露糖n -聚糖特异性凝集素家族和多功能低分子量多肽凝集素家族。对于高甘露糖n -聚糖特异性凝集素家族，首先，研究了红藻Eucheuma serra凝集素（ESA-2）的详细碳水化合物结合特异性和初级结构。接下来，我们发现口服ESA-2抑制了1,2-二甲基肼小鼠结肠异常隐窝灶的形成，这是由于结肠组织中活性氧的产生较低。与此相关，利用一种新建立的分离细胞膜受体的方法，在人结肠癌培养细胞（HT-29）上鉴定出ESA-2受体。此外，还研究了该家族的一种蓝藻凝集素（OAA）的初级结构和详细的碳水化合物结合特异性。此外，该家族的某些凝集素可作为亲和配体一步纯化用于牛海绵状脑病（BSE）诊断的鸡单克隆抗体。在一个多功能低分子量多肽凝集素家族中，我们发现来自红藻Hypnea japonica的凝集素（hypnin a）对n -聚糖中的核心α1-6病灶具有严格的特异性，可以作为检测癌症标志物的试剂，并可制备缺乏核心α1-6病灶的具有有效抗体依赖性细胞毒性（ADCC）的药用抗体。