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

我们对这四个课题进行了研究，得到的结果如下：(1)我们成功合成了2'-0,4'- c -亚甲基桥接的核酸类似物（BNAs）和含有BNA的寡核苷酸（BNA- odns）。发现bna - odn比天然odn和改性odn具有更有效的双工和三工形成能力。将bna - odn与天然odn和s - odn的各种性质进行比较，表明bna - odn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，这些化合物被发现对α-氨基酯和n端肽的不对称α-烷基化有效。采用吡哆醛模型化合物也成功地实现了丝氨酸衍生物与硫醇的β取代催化反应。(3)我们合成了具有杂环结构的萤火虫荧光素类似物，取代了萤火虫荧光素分子的苯并噻唑结构，并研究了它们的生物发光和化学发光活性。结果发现，苯并咪唑衍生物在荧光素酶处理下表现出有效的发光，而苯并恶唑衍生物在氧化处理下表现出有效的化学发光。(4)合成了具有对称结构的阳离子脂质，并对其脂质体的基因转染活性进行了研究。结果发现，由对称结构的脂质体组成的脂质体比具有不对称结构的脂质体更容易制备，并且具有低毒和有效的基因转染效果。

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.