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.

我们研究了四个受试者，并获得了下面所示的结果：（1）我们成功地合成了2'-0,4'-C-甲基桥接的核酸类似物（BNA）和含有BNA（BNA-ODNS）的寡核苷酸。发现BNA-ODN具有比天然ODN的更有效的双链体和三重形成能力，并且有报道的ODN。 BNA-ODN与天然ODN和S-ODN的各种特性的比较表明，BNA-ODN具有出色的反义能力。（2）。我们已经设计和合成了具有手性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，发现它们对N端位置的α-氨基酯和Petides的非对称α-烷基化有效。通过采用吡啶还毒模型化合物，成功实现了Ser衍生物与硫醇的催化β替代反应。（3）我们已经合成了具有异性烯烃结构的飞行荧光素荧光素类似物，代替了代替氟利夫蛋白的苯并素结构，并对其进行了介绍，并对其进行了介绍，并对其进行了研究。结果，发现苯咪唑衍生物通过用荧光素酶处理显示有效的光 - emmisio，而苯唑唑衍生物对氧化处理诱导的化学发光有效。（4）我们已经合成具有对乳液制成的基因结构和研究的Liposome contranceed liposome的阳离子性脂质。因此，发现由对称脂质组成的脂质体比具有不对称结构的脂质更容易制备，对基因转化是低毒性且有效的。