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，我们检查了从珊瑚礁暮光区收集的海洋无脊椎动物的代谢产物，可以将其定义为40 m至150 m.a的深度范围M.a的亲脂性suberites suberites japonicus japonicus japonicus japonicus显示出强的细胞毒性强度。分离后，通过分析其光谱数据和制作衍生物来获得一系列名为Sergamides A-F的细胞毒素。作为Seragamide A抑制的培养细胞的细胞动物SI，怀疑该分子可能靶向细胞骨架蛋白肌动蛋白。通过使用荧光标记的1肌动蛋白，我们可以证实Seragamide抑制了F-肌动蛋白的解聚并促进G-肌动蛋白的聚合。这种作用方式类似于鬼笔环肽和Jaspamide的作用方式。海绵dysidea cf.发现竞技场含有中等的细胞毒素。通过将其提取物分开，我们完全获得了具有海绵级骨骼的七个新的二萜。通过解释其NMR数据以及将数据与报告的数据进行比较来阐明它们的结构。在这项研究中，我们发现海绵旁二烯烯具有收集位点的变化。在Kunigami村收集，被发现包含新的Briarane类二萜。其中一些被证明是细胞因子抑制剂。此外，我们从冲绳岛的珊瑚礁暮光区完全收集了44个海洋无脊椎动物标本，并在筛选后获得了几个已知的生物活性分子。由于这项研究仍然是一个正在进行的项目，我希望我们可以将更多新的生物活性分子与它们隔离开来。