|Budget Amount *help
¥5,300,000 (Direct Cost: ¥5,300,000)
Fiscal Year 1991: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1990: ¥4,500,000 (Direct Cost: ¥4,500,000)
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.