27 核酸結合性ポリアミン-フラーレン複合体の合成と機能(口頭発表の部)

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Much interest in the biological acitities of fullerenes have been drawn since their first discovery. As one of the first findings of biological activities, we have already reported the synthesis of water-miscible fullerene carboxylic acid and its biological activities. Thus, we found that fullerenes show the photo-induced DNA cleaving activity, cytotoxicity and enzyme inhibition. In this study, we further investigated their biological activities, including distribution analysis of dosed radio-active fullerene and interactions with DNAs. We have synthesized radio-active water-miscible fullerene carboxylic acid by [3+2] cycloaddition of trimethylene methane. When administered orally to rats, fullerene was not efficiently absorbed and was excreted primarily in the feces. When injected itravenously, it was distributed rapidly to various tissues, and most of the material was retained in the body after one week. We have expanded fullerene's photo-induced biological activities, targeting DNAs. Thus, we have designed and synthesized a novel fullerene-oligonudeotide conjugate, and examined its DNA nicking ability. When this conjugate was incubated and irradiated with oligonuculeotides with target sequence, site specific nicking of the oligonuleotide was achieved. We further continued investigating the interactions of fullerene with DNAs and found that fullerene-polyamine conjugate tightly binds to DNA in a non-specific manner, and this new fullerene gave first example of photoinduced covalent bond formation of fullerene with DNA base.
天然有機化合物討論会の論文
1998-08-31

27 核酸結合性ポリアミン-フラーレン複合体の合成と機能(口頭発表の部)

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