Preparation of Functional Polylipid Biofactors

分析了亲水环境下控制基因表达和细胞增殖的脂类生物因子的行为。各种脂质生物因子，包括dna插入物、类维生素a、肿瘤启动子和核碱基被选为分子进行分析。通过右旋糖酐偶联法和/或使用镜像核苷酸将它们转化为水溶性物质。通过引入荧光和/或光不稳定的官能团，选定的化合物被多功能化。使用插入物-葡聚糖方法分析发现插入物与单/二核苷酸具有非插入性碱基选择性相互作用。利用镜像核苷酸，即对映体/中位dna进行分析，揭示了这些伪dna与互补的天然核酸的特征相互作用。结果表明，这些伪dna可以作为新的反义/抗原分子的先导化合物。荧光/光降解性合成类维甲酸的发展达到了对核维甲酸受体配体结合区域中配体直接相互作用位点的阐明。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。与肿瘤启动子配位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。

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.