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Search for mole cular probes from non-utilized marine resources of coral reef twilight zone

从珊瑚礁暮色带未利用海洋资源中寻找分子探针

基本信息

批准号：
16550145
负责人：
TANAKA Junichi
金额：
$ 2.11万
依托单位：
University of the Ryukyus
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

项目摘要

In order to discover new bioactive molecules, we examined metabolites of marine invertebrates collected from the coral reef twilight zone, where can be defined as depth range between 40 m and 150 m.A lipophilic extract of the sponge Suberites japonicus showed strong cytotoxicity,. After separation, a series of cytotoxins named sergamides A-F were obtained by analyzing their spectroscopic data and by making derivatives. As seragamide A inhibited cytokinc sis of cultured cells, it was suspected that the molecule might target the cytoskeletal protein actin. By using fluorescent-labeled 1 actin, we could confirm that seragamide A inhibited depolymerization of F-actin and facilitated polymerization of G-actin. This mode of action was similar to those of phalloidin and jaspamide. The sponge Dysidea cf. arenaria was found to contain moderate cytotoxins. By separating its extract, we obtained totally seven new diterpenes having spongian class skeleton. Their structures were elucidated by interpreting their NMR data and also by comparing the data with those reported. During this study we found that there exists variation on the spongian diterpenes with collection sites.A gorgonian coral Ellisella sp. was collected at Kunigami village and was found to contain new briarane class diterpenes. Some of them was shown to be cytokinesis inhibitors.In addition, we collected totally 44 specimens of marine invertebrates from the coral reef twilight zone along Okinawa Island, and obtained several known bioactive molecules after screening. As this research is still an on-going project, I hope we can isolate more new bioactive molecules from them.

为了发现新的生物活性分子，我们研究了从珊瑚礁黄昏地带采集的海洋无脊椎动物的代谢物，这里的深度范围在40米到150米之间。分离后，通过对其光谱数据的分析和衍生物的制备，得到了一系列的细胞毒素，命名为丝氨酰胺A-F。由于丝氨酰胺A抑制了培养细胞的细胞分裂，推测该分子可能针对细胞骨架蛋白肌动蛋白。通过荧光标记的肌动蛋白1，我们可以证实，丝氨酸胺A抑制了F-肌动蛋白的解聚，促进了G-肌动蛋白的聚合。这种作用模式类似于鬼臼草素和茉莉花胺。海绵Dyside a cf.海参中含有中等含量的细胞毒素。通过对其提取物的分离，共得到7个具有支链类骨架的新二萜类化合物。通过解释它们的核磁共振数据，并与文献报道的数据进行比较，确定了它们的结构。在本研究中，我们发现海绵二萜类化合物随采集点的不同而存在差异。在库尼加米村采集，发现含有新的布瑞烷类二萜类化合物。此外，我们从冲绳岛珊瑚礁暗带采集了44个海洋无脊椎动物标本，经过筛选得到了几个已知的生物活性分子。由于这项研究仍在进行中，我希望我们能从它们中分离出更多新的生物活性分子。