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Development and mode of action of inhibitors of macromolecule biosynthesis from marine animals.

海洋动物大分子生物合成抑制剂的开发及其作用方式。

基本信息

批准号：
09460057
负责人：
IKEGAMI Susumu
金额：
$ 5.12万
依托单位：
HIROSHIMA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

项目摘要

During the course of our screening program for inhibitors of starfish (Asterina pectinifera) embryonic development from marine organisms, we found that the MeOH extract of the marine sponge Rhopaloeides sp. inhibited starfish embryogenesis specifically at the stage prior to gastrulation. A preliminary examination led to the isolation of an unusual norsesterterpene designated rhopaloic acid A which inhibited gastrulation of the starfish embryo and exhibited potent cytotoxicities against human myeloid K-562 cells, human MOLT-4 leukemia cells, and murine L1210 leukemia cells7. Further investigation of the extract of Rhopaloeides sp. led to the isolation of related metabolites, rhopaloic acids B and C.We determined the structure and uncovered biological activities of these compounds.We discovered a novel nucleic-acid associated protein designated as NAAP which was isolated from starfish oocytes. Oligonucleotides derived from the partial amino acid sequences of NAAP were used to clone NAAP cDNA and the entire cDNA sequence was determined. The transcript encoding NAAP was present only in growing oocytes but not in full-grown oocytes, embryos and adult tissues. The NAAP protein localized in the germinal vesicle of the full-grown oocyte and dispersed diffusely after germinal vesicle breakdown at the onset of meiosis. During oocyte maturation, NAAP changed the molecular form in a cell-cycle dependent manner. It was found that Ser 145 of NAAP, which was unphosphorylated at the germinal vesicle stage, was phosphorylated during the M phase of meiosis.

在我们从海洋生物中筛选海星(Asterina Pectinifera)胚胎发育抑制物的过程中，我们发现海绵Rhop aloedes sp.的甲醇提取物。在原肠形成之前的阶段特异性地抑制海星胚胎的发生。初步检查导致分离出一种不寻常的去甲萜酸A，它抑制海星胚胎的原肠形成，并对人髓系K-562细胞、人MOLT-4白血病细胞和小鼠L1210白血病细胞表现出强大的细胞毒活性。金龟子提取液的进一步研究从海星卵母细胞中分离出一种新的核酸相关蛋白NAAP。从NAAP的部分氨基酸序列中提取寡核苷酸，克隆NAAP的cDNA，并测定其全序列。编码NAAP的转录本只在发育中的卵母细胞中存在，而在完全发育的卵母细胞、胚胎和成体组织中不存在。NAAP蛋白定位于成熟卵母细胞的生发泡，并在减数分裂开始时生发泡破裂后弥散分布。在卵母细胞成熟过程中，NAAP以细胞周期依赖的方式改变了分子形式。结果发现，NAAP的Ser145在生发泡期未被磷酸化，在减数分裂的M期被磷酸化。