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C-P compounds, biological activities and medical uses.

C-P 化合物、生物活性和医疗用途。

基本信息

批准号：
04304049
负责人：
SATAKE Mei
金额：
$ 5.12万
依托单位：
Niigata University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Co-operative Research (A)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1993
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-04304049/
关键词：
C-P compounds Glycolipids Nervous tissues Antibiotics Enzymatic synthesis of C-P bond Genes Chemical synthesis of C-P compounds

项目摘要

Since Horiguchi and Kandatsu first isolated natural C-P compound, 2-aminoethyl-phosphonate, much work has been carried out in Japan. Theme of the present 2-years project were (1) isolation and identification, (2) tissue distribution, (3) biological activities, (4) biosynthesis and (5) chemical synthesis of the C-P compounds.Following results were obtaied : (Theme 1) Several new C-P sphingoglycolipids were isolated from protostomia. Their carbohydrate and oligosaccharide structures were different from those of deuterostomia. A glycolipid had one mole each of 2-aminoethylphosphonate (C-P) and phosphoethanolamine (C-O-P) which suggests a way of molecular evolution of sphingoglycolipid species. (Theme 2) antiphosphonoglycocerebroside antisera specifically stain nervous tissues of crustacea. (Theme 3) C-P sphingoglycolipids isorated from Aplysia activated cAMP-dependent protein kinase by binding to the catalytic subunit of the enzyme. (theme 4) Genes of phosphoenolpyruvic acid (PnPy) phosphomutase and PnPy decarboxylase which were key enzymes for the synthesis of fosfomycin were cloned and a gene of p-methylating enzyme for the synthesis of C-P-C bond of bialaphos was cloned. (Theme 5) Oxygen of hemiacetal ring of sugar was replaced by phosphorus by sophisticated methods and many novel C-P compounds were chemically synthesized. Some of them were biologically active.

自Horiguchi和Kandatsu首次分离出天然C-P化合物2-氨基乙基膦酸酯以来，在日本进行了大量的工作。本课题对C-P鞘糖脂的分离鉴定、组织分布、生物活性、生物合成和化学合成等方面进行了研究，取得了以下成果：（1）从原口线虫中分离到几种新的C-P鞘糖脂。它们的碳水化合物和寡糖结构与后口动物不同。糖脂含有1摩尔的2-氨基乙基膦酸酯（C-P）和磷酸乙醇胺（C-O-P），这表明鞘糖脂物种的分子进化方式。（主题2）抗磷酸苷抗血清特异性染色甲壳动物的神经组织。（主题3）C-P鞘糖脂是从Astrasia中分离出来的，它通过与cAMP依赖性蛋白激酶的催化亚基结合而激活cAMP依赖性蛋白激酶。（主题4）克隆了磷霉素合成关键酶磷酸烯醇式酸（PnPy）磷酸变位酶和PnPy脱羧酶基因，并克隆了双丙氨磷C-P-C键合成的P-甲基化酶基因。（主题5）通过复杂的方法将糖的半缩醛环上的氧替换为磷，合成了许多新颖的C-P化合物。其中一些具有生物活性。