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

寻找可用于Ca^<2>信号转导研究的海洋生物活性物质

基本信息

批准号：
02453138
负责人：
KOBAYASHI Jun'ichi
金额：
$ 3.39万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1991
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-02453138/
关键词：
Ca signal transductions marine bioactive substances Ca^<2+> inducer actomyosin ATPase activator calmodulin antagonist protein kinase C activator sponge tunicate 筋小胞Ca遊離促進物質 Cーキナ-ゼ活性化物質アクトミオシンATPase活性化物質海洋生物

项目摘要

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.

在该研究项目中，我们研究了冲绳海洋生物的生物活性物质，以找到有用的化合物，这些化合物激活或抑制重要蛋白质的活性，例如CA-CHANNEN，CA-ATPase，ca-atpase，Actomyosin atpase，钙调蛋白，钙调蛋白和蛋白质激酶。这些蛋白质具有重要的角色。在细胞内Ca^<2+>信号转导中，从海绵theonella sp中获得了抑制肌肉经典网状ca^<2+> atpase的活性的环状肽。作为肌动蛋白ATPase激活剂，丙烯磷酸蛋白和氧化蛋白二聚体溴吡咯生物碱是从艾agelas属的海绵中分离出来的。刚性吡啶素，一种吡咯吡汀生物碱，来自肌张力蛋白蛋白酶cf。 Rigida和Konbamide是一种环状肽，来自海绵theonella sp。表现出钙调蛋白的拮抗活性。 Iejimalides C和D，24元的大花环硫酸盐，是从punicate eudistoma cf中分离出来的。 Rigida作为蛋白激酶C活化剂。这些化合物的化学结构是根据广泛的光谱数据阐明的。在这些化合物中，Iejimalides C和D特别是独特的，因为这些大花环的一部分结构变化会引起对蛋白激酶C的影响的变化，从。因此，Iejimalides C和D被期望是理解蛋白激酶C的分子作用机理的有用工具。