Search for marine bioactive substances useful for studies of Ca^<2+> signal transductions

在本研究项目中，我们研究了冲绳海洋生物的生物活性物质，以寻找激活或抑制重要蛋白质（如Ca通道、Ca-ATP酶、肌动球蛋白ATP酶、钙调蛋白和蛋白激酶C）活性的有用化合物。Keramamide A是从海绵Theonella sp.中分离得到的一种环肽，可抑制肌浆网Ca^2 +-ATP酶的活性。作为肌动球蛋白ATP酶的激活剂，从Agelas属海绵中分离得到ageliferins和oxyceptrin，即二聚溴吡咯生物碱。Rigidin是一种吡咯并嘧啶生物碱，来自被囊类Eudistoma cf. rigida和来自海绵Theonella sp.的环肽konbamide表现出钙调素拮抗活性。Iejimalides C和D，24元大环内酯硫酸酯，从被囊类Eudistoma cf. rigida作为蛋白激酶C激活剂。这些化合物的化学结构经大量光谱数据鉴定，其中尤以艾吉马利内酯C和D最为独特，因为这些大环内酯的一部分结构变化引起对蛋白激酶C的作用由激活变为抑制。因此，Iejimalides C和D有望成为了解蛋白激酶C作用的分子机制的有用工具。

In this research project we studied bioactive substances from Okinawan marine organisms to find useful compounds that activate or inhibit the activities of important proteins such as Ca-channel, Ca-ATPase, actomyosin ATPase, calmodulin, and protein kinase C. These proteins have crucial roles in intracellular Ca^<2+> signal transductions.Keramamide A, a cyclic peptide which inhibits the activity of sarcoplassic reticulum Ca^<2+>-ATPase, was obtained from a sponge Theonella sp. As actomyosin ATPase activators, ageliferins and oxysceptrin, dimeric bromopyrrole alkaloids, were isolated from sponges of the genus Agelas. Rigidin, a pyrrolopyrimidine alkaloid, from a tunicate Eudistoma cf. rigida, and konbamide, a cyclic peptide, from a sponge Theonella sp. exhibited calmodulin antagonistic activity. Iejimalides C and D, 24-membered macrolide sulfates, were isolated from a tunicate Eudistoma cf. rigida as protein kinase C activators. The chemical structures of These compounds were elucidated on the basis of extensive spectroscopic data.Among these compounds, iejimalides C and D are especially unique since structural change of a part of these macrolides induces a change of the effect against protein kinase C from activation to inhibition. Iejimalides C and D are therefore expected as a useful tool for understanding the molecular mechanism of action of protein kinase C.