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Microtubulin assembly inhibitors from microorg origin

来自微生物来源的微管蛋白组装抑制剂

基本信息

批准号：
63560130
负责人：
KOBAYASHI Akio
金额：
$ 1.34万
依托单位：
Faculty of Agriculture, OKAYAMA University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1988
资助国家：
日本
起止时间：
1988 至 1989
项目状态：
已结题

项目摘要

Several cell organelles assembled from microtubules (MTs) and other proteins perform an important role in cell biology. MTs are found in a great variety of situations in cells, and may occur singly, loosely ordered into bundles, or in highly ordered arrays of a define pattern. These variations are presumably related to the different functions of MTs. In order to understand such functions, several naturally occurring compounds have been used as molecular probes. T-1 and curvularin have been found to be effective mitotic inhibitors which induced barrel-shaped spindles in sea urchin eggs due to disorder of the microtubule organising centers ( MTOCs) in centrosomes. MTs are also involved in the pronuclear fusion (PF) of sea urchin eggs. Early literature contains few reports of this process, and a better understanding of the detailed role and nature of MTs awaits the discovery of new types of specific inhibitors toward PF. We made the first systematic search for microbial products that might have PF inhibitory activity using a novel bioassay system. A Streptomyces sp. K02388 was discovered, which produced a novel gamma-pyrone, named streptopyrone with pronounced inhibitory activity toward PF. A fungus, Curvularia harveyi, was found to produce a new mitotic arrester, which was named harveynone and its structure was elucidated. This compound effectively inhibited spindle formation and arrested the first cell division of sea urchin eggs. The mode of operation of these compounds are in progress.

由微管 (MT) 和其他蛋白质组装而成的几种细胞器在细胞生物学中发挥着重要作用。 MT 在细胞中存在于多种情况下，并且可能单独出现、松散地排列成束或以定义模式的高度有序阵列出现。这些变化可能与 MT 的不同功能有关。为了理解这些功能，几种天然存在的化合物已被用作分子探针。 T-1 和 curvularin 被发现是有效的有丝分裂抑制剂，由于中心体微管组织中心 (MTOC) 紊乱，可诱导海胆卵形成桶状纺锤体。 MT 还参与海胆卵的原核融合 (PF)。早期文献对此过程的报道很少，对 MT 的详细作用和性质的更好理解有待发现新型 PF 特异性抑制剂。我们使用新型生物测定系统首次系统地搜索可能具有 PF 抑制活性的微生物产品。链霉菌属 (Streptomyces sp.) K02388被发现，它产生一种新型的γ-吡喃酮，命名为链吡喃酮，对PF具有明显的抑制活性。人们发现一种名为哈维弯孢菌（Curvularia harveyi）的真菌能够产生一种新的有丝分裂抑制剂，并将其命名为哈维酮（harveynone），并阐明了其结构。这种化合物有效抑制纺锤体形成并阻止海胆卵的第一次细胞分裂。这些化合物的操作模式正在进行中。