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

• 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

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。

项目成果

Kobayashi,J.: "Konbamide,a novel peptide with calmodulin antagonistic activity from the Okinawan marine sponge Theonella sp." J.Chem.Soc.,Chem.Commun.1050-1052 (1991)

Kobayashi,J.：“Konbamide，一种来自冲绳海绵 Theonella sp. 的具有钙调蛋白拮抗活性的新型肽。”

Kikuchi, Y.: ""Iejimalides C and D, new antineo-plastic 24-member macrolide sulfates from the Okinawan marine tunicate Eudistoma cf. rigida. "" Tetrahedron Lett.32. 797-798 (1991)

Kikuchi, Y.：“Iejimalides C 和 D，来自冲绳海洋被囊动物 Eudistoma 的新型抗肿瘤 24 元大环内酯硫酸盐，参见。

Kobayashi,J.: "Ageliferins,potent actomyosin ATPase activators from the Okinawan marine sponge Agelas sp." Tetrahedron. 46. 5579-5586 (1990)

Kobayashi,J.：“Ageliferins，来自冲绳海绵 Agelas sp 的有效肌动球蛋白 ATP 酶激活剂。”

Kobayashi, J.: ""Keramamide A, a novel peptide from the Okinawan marine sponge Theonella sp. "" J. Chem. Soc., Perkin Trans. l. 2609-2611 (1991)

Kobayashi, J.：“Keramamide A，一种来自冲绳海绵 Theonella sp. 的新型肽。

Kobayashi,J.: "Keramamide A,a novel peptide from the Okinawan marine sponge Theonella sp." J.Chem. Soc.,Perkin Trans.1. 2609-2611 (1991)

Kobayashi,J.：“Keramamide A，一种来自冲绳海绵 Theonella sp. 的新型肽。”