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

本研究旨在阐明海藻凝集素的生物活性、分子机制和构效关系，特别是属于高甘露糖N-糖特异性凝集素家族或多功能低分子多肽凝集素家族的凝集素。对于高甘露糖N-糖特异性凝集素家族，首先阐明了红藻Eucheuma Serra Lectin(ESA-2)的糖结合专一性和一级结构。其次，研究发现，口服ESA-2可抑制1，2-二甲基肼所致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减少所致。与此相关的是，用一种新建立的细胞膜受体分离方法鉴定了人结肠癌培养细胞(HT-29)上的ESA-2受体。此外，还阐明了属于该家族的蓝藻Oscillatoria agardhii Lectin(OAA)的一级结构和详细的碳水化合物结合专一性。此外，一些属于该家族的凝集素被证明是非常有用的亲和配体，用于一步纯化可用于诊断牛海绵状脑病的鸡单抗。针对一个多功能的低分子多肽凝集素家族，研究发现，从红藻中提取的凝集素(菌丝素A)严格特异于N-糖链中的核心α1-6岩藻糖，可用作检测癌症标志物(S)的试剂，以及制备缺乏核心α1-6岩藻糖的药物抗体。

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)