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

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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.