Preparation of Functional Polylipid Biofactors

功能性多脂生物因子的制备

• 批准号: 06557118
• 负责人: HASHIMOTO Yuichi
• 金额: $ 5.7万
• 依托单位: THE UNIVERSITY OF TOKYO
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06557118/
• 关键词: dextran; intercalator; retinoid; porphyrin; affinity labeling; nucleic acid; receptor; tumor promoter; 分子認識; インターカレーション; ジヌクレオチド; 塩基選択性; 水溶性ポリマー; ヘミン

Behavior in hydrophyilic circumstances of lipid biofactors which control gene expression and sell proliferation was analyzed. Various lipid biofactors including DNA-intercalators, retinoids, tumor promoters, and nuclobases were selected as molecules which to be analyzed. They were converted to water-soluble materials by the dextran-coupling method and/or the usage of the mirror-image nucleosugar. Selected compounds were polyfunctionalized by introducing fluorescent and/or photolabile functioal groups.Analysis using the intercalator-dextran method revealed non-intercalative base-selective interaction of the intercalator and mono/di-nucleotides.Analysis using the mirror-image nucleosugar, i. e., enantio/meso-DNAs, revealed the characteristic interactions of these pseudo-DNAs with the complementary natural nucleic acids. The results suggest that these pseudo-DNAs can be lead compounds for new antisense/antigene molecules.Development of fluorescent/photolablile synthetic retinoids reached to the elucidation of the sites in nuclear retinoic acid receptor's ligand binding domain at which the ligand directly interacts. Similar technique applied on tubulin disruptors revealed the sites in tubulin protein at which the disruptors directly interact.Preparation of affinity gels liganded with tumor promoters reached the purification of the putative specific tumor promoter receptor whose structural identification is under progress.

分析了控制基因表达和细胞增殖的脂质生物因子在亲水环境下的行为。选择各种脂质生物因子作为待分析的分子，包括DNA嵌入剂、类维生素A、肿瘤启动子和核碱基。通过葡聚糖偶联方法和/或使用镜像核糖将它们转化为水溶性材料。通过引入荧光和/或光不稳定的官能团，对选定的化合物进行多官能化。使用嵌入剂-葡聚糖方法的分析揭示了嵌入剂和单/二核苷酸的非嵌入碱基选择性相互作用。使用镜像核糖的分析，即。例如，对映体/内消旋 DNA，揭示了这些假 DNA 与互补的天然核酸的特征相互作用。结果表明这些假DNA可以作为新反义/抗原分子的先导化合物。荧光/光不稳定合成类维生素A的开发达到了阐明核视黄酸受体的配体结合结构域中配体直接相互作用的位点。类似的技术应用于微管蛋白干扰物，揭示了微管蛋白中干扰物直接相互作用的位点。与肿瘤启动子配体的亲和凝胶的制备达到了假定的特异性肿瘤启动子受体的纯化，其结构鉴定正在进行中。

项目成果

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桥本雄一：“镜子的 DNA”数学科学。 33. 53-58 (1995)

Y.Shibata, M.Shichita, K.Sasaki, K.Nishimura, Y.Hashimoto, S.Iwasaki N-Alkylphthalimides: "Structural requirement of thalidomidal action." Chem. Pharm. Bull.43. 177-179 (1995)

Y.Shibata、M.Shichita、K.Sasaki、K.Nishimura、Y.Hashimoto、S.Iwasaki N-烷基邻苯二甲酰亚胺：“沙利度胺作用的结构要求。”

T.Sasaki, R.Shimazawa, T.Sawada, T.Iijima, H.Fukasawa, K.Shudo, Y.Hashimoto, S.Iwasaki: "Determination of the photoaffinity-labeled site on the ligand-binding domain of human retinoic acid receptor alpha" Biochem. Biophys. Res. Commun.207. 444-451 (1995)

T.Sasaki、R.Shimazawa、T.Sawada、T.Iijima、H.Fukasawa、K.Shudo、Y.Hashimoto、S.Iwasaki：“人视黄酸配体结合域上光亲和标记位点的测定

O.Nakajima, M.Shichita, S.Iwasaki, Y.Hashimoto: "Application of the dextran-coupling method for analysis of interactions between intercalators and nucleotides." Nucl. Acids Symp. Ser.34. 137-138 (1995)

O.Nakajima、M.Shichita、S.Iwasaki、Y.Hashimoto：“应用葡聚糖偶联方法分析嵌入剂和核苷酸之间的相互作用。”