Design and Syntheses of Biologically Functional Molecules Based on the Mechanisms of Life

基于生命机制的生物功能分子的设计与合成

基本信息

批准号：
11470469
负责人：
IMANISHI Takeshi
金额：
$ 7.55万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

项目摘要

We studied the four subjects and obtained the results shown below:(1) We have succeeded to synthesize 2'-0,4'-C-methylene bridged nucleic acid analogs (BNAs) and oligonucleotides containing the BNA (BNA-ODNs). The BNA-ODNs were found to have more effective duplex and triplex forming ability than natural ODNs and modified ODNs ever reported. Comparison of various properties of BNA-ODNs with those of natural ODNs and S-ODNs showed that the BNA-ODNs have an excellent antisense ability.(2). We have designed and synthesized novel chiral vitamin B_6 model compounds having a chiral ansa-structure and/or a chiral ionophore structure, which were found to be effective for asymmetric α-alkylation ofα-amino esters and petides at the N-terminal position. Catalytic β-replacement reaction of a Ser derivative with thiols was also successfully achieved by employing the pyridoxal model compounds.(3) We have synthesized fire-fly luciferin analogs having a heterocyclic structure in place of the benzothiazole structure of the fire-fly luciferin molecule, and studied their bioluminescent and chemiluminescent activities. As a result, it was found that the benzimidazole derivative shows effective light-emmisio by treatment with luciferase, while the benzoxazole derivative is effective for chemiluminescent induced by oxidative treatment.(4) We have synthesized cationic lipid having a symmetrical structure, and studied gene transfection activity of liposome prepared from the lipid. As a consequence, it was found that the liposome composed of the symmetrical lipid, which was more easily prepared than that having an unsymmetrical structure, is low toxic and effective for gene transfection.

我们对四个课题进行了研究，得到如下结果：(1)我们成功合成了2'-0,4'-C-亚甲基桥核酸类似物(BNA)和含有BNA的寡核苷酸(BNA-ODN)。发现-ODN 比天然 ODN 和已报道的修饰 ODN 具有更有效的双链体和三链体形成能力，并将 BNA-ODN 的各种特性与天然 ODN 的性能进行比较。 S-ODNs表明BNA-ODNs具有优异的反义能力。(2)我们设计并合成了具有手性ansa结构和/或手性离子载体结构的新型手性维生素B_6模型化合物，并被发现是有效的。 α-氨基酯和肽在 N 端位置的不对称 α-烷基化 Ser 衍生物与硫醇的催化 β-取代反应也成功实现。 (3)我们合成了具有杂环结构的萤火虫荧光素类似物来代替萤火虫荧光素分子中的苯并噻唑结构，并研究了它们的生物发光和化学发光活性。苯并咪唑衍生物通过荧光素酶处理显示出有效的发光，而苯并恶唑衍生物对化学发光诱导有效(4)合成了具有对称结构的阳离子脂质，并研究了由该脂质制备的脂质体的基因转染活性，发现由对称脂质组成的脂质体更容易制备。与不对称结构相比，其毒性低且对基因转染有效。