Preparation of Functional Polylipid Biofactors

分析了控制基因表达和细胞增殖的脂类生物因子在亲水环境中的行为。选择各种脂质生物因子，包括DNA嵌入剂、类维生素A、肿瘤促进剂和核纤酶作为待分析的分子。它们通过葡聚糖偶联方法和/或镜像核糖的使用转化为水溶性材料。通过引入荧光和/或光不稳定的功能基团，选择性地将化合物多功能化，用嵌入剂-葡聚糖方法分析表明嵌入剂和单/双核苷酸的非嵌入碱基选择性相互作用。例如，对映体/内消旋-DNA，揭示了这些假DNA与互补天然核酸的特征性相互作用。这些结果表明，这些假DNA可以作为新的反义/抗基因分子的先导化合物，荧光/光致变色合成类视黄酸的发展达到了阐明视黄酸受体的配体结合域中配体直接相互作用的位点。将类似的技术应用于微管蛋白干扰物上，揭示了微管蛋白中干扰物直接相互作用的位点，制备了与肿瘤启动子配体的亲和凝胶，实现了对推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。

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.