Development of Biochemical Reagents to Study Signal Transduction from Awuatic Organisms

我们收集了日本沿海沿着的海洋无脊椎动物，并进行了生物活动筛选。根据筛选结果，我们分离和表征了活性成分，并研究了它们的作用方式，这可能会导致生化试剂的发展。1.新活性代谢物的分离和结构鉴定从八丈岛海域采集的海绵Theonella swinhoei中，我们分离到了新的丝氨酸蛋白酶抑制剂，pseudotheonamides，它们与已知的具有不同环化模式的环theonamides有关。从海绵Stelletta globostellatta中分离出三种新的isomalabaricane三萜，其诱导大鼠3 Y1成纤维细胞的形态学变化。我们还研究了这些三萜类化合物之间的构效关系。从硬海绵属（Xestospongia）和双齿海绵属（Amphimedon）海绵中分离得到7个3-烷基吡啶生物碱。从花萼盘皮菌（Discodermia calyx）中分离得到新的花萼素衍生物。研究了化学修饰衍生物和新型天然calyculins对蛋白磷酸酶的抑制作用，并建立了一定的构效关系.利用海绵生物碱xestospongin C抑制IP_3与其受体的结合，研究了Ca ~（2+）参与豚鼠乳头肌收缩的作用。

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.