Development of Biochemical Reagents to Study Signal Transduction from Awuatic Organisms

我们在日本沿海采集了海洋无脊椎动物，并进行了生物活动的筛选。根据筛选结果，我们对活性成分进行了分离和表征，并研究了它们的作用方式，这可能会导致生化试剂的开发。新的生物活性代谢产物的分离和结构鉴定从八条吉马岛外采集的海绵Theonella swinhoei中，我们分离到了新的丝氨酸蛋白酶抑制剂--假香草酰胺，它们与已知的具有不同环化方式的环香酰胺类化合物有关。从瑞香狼毒海绵中分离得到三个新的异杏仁烷三萜类化合物，它们能引起大鼠3Y1成纤维细胞的形态改变。我们还研究了这些三萜类化合物之间的构效关系。从海绵属植物Xestospongia和Amphimedon中分离得到7个3-烷基吡啶生物碱。从花瓣盘皮中分离得到新的花蕾素衍生物。研究了化学修饰的衍生物和新型天然毛盏花素对蛋白磷酸酶的抑制作用，并建立了一些构效关系。海绵生物碱xestospongin C抑制IP3与其受体结合、钙离子参与豚鼠乳头状肌收缩的作用模式研究

We have collected marine invertebrates along the coast of Japan and carried out screening for biological activities. Based on the results of the screening we have isolated and characterized the active principles and studied their modes of action, which may lead to the development of biochemical reagents.1. Isolation and structure elucidation of novel bioactive metabolitesFrom the marine sponge Theonella swinhoei collected off Hachijo-jima Island, we have isolated novel serine protease inhibitors, pseudotheonamides, which were related to the known cyclotheonamides with different modes of cyclization. From the sponge Stelletta globostellatta were isolated three novel isomalabaricane triterpenes which induce morphological changes in rat 3Y1 fibroblasts. We also examined the structure-activity relationships among these triterpenes. Seven 3-alkylpyridine alkaloid were isolated from sponges of genera Xestospongia and Amphimedon. Novel calyculin derivatives were isolated from Discodermia calyx. Chemically modified derivatives and novel natural calyculins were examined for their effects against protein phosphatases and some structure-activity relationships were established.2. Studies on the modes of action of bioactive marine natural productsBy using a sponge-derived alkaloid xestospongin C which inhibits the binding of IP3 to its receptor, the involvement of Ca ions in the contraction of guinea-pig papillary muscle.