九州大学 研究者情報
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基本情報 研究活動 教育活動 社会活動
阿部 由紀子(あべ ゆきこ) データ更新日:2019.04.22

助教 /  薬学研究院 創薬科学部門 医薬化学


主な研究テーマ
DNA損傷を特異的に認識できる分子の開発
キーワード:特異的認識、DNA損傷、結合分子
2008.04.
自己切断能を有する機能性プローブの開発
キーワード:検出、特異的認識、触媒サイクル
2006.04~2008.03.
研究業績
主要原著論文
1. 阿部 由紀子, 佐々木 茂貴, DNA cleavage at the AP site via b-elimination mediated by the AP site-binding ligands, Bioorganic & Medicinal Chemistry, 24, 4, 910-914, 2016.01, DNA is continuously damaged by endogenous and exogenous factors such as oxidation and alkylation. In the base excision repair pathway, the damaged nucleobases are removed by DNA N-glycosylase to form the abasic sites (AP sites). The alkylating antitumor agent exhibits cytotoxicity through the formation of the AP site. Therefore blockage or modulation of the AP site repair pathway may enhance the antitumor efficacy of DNA alkylating agents. In this study, we have examined the effects of the nucleobase-polyamine conjugated ligands (G-, A-, C- and T-ligands) on the cleavage of the AP site. The G- and A-ligands cleaved DNA at the AP site by promoting β-elimination in a non-selective manner by the G-ligand, and in a selective manner for the opposing dT by the A-ligand. These results suggest that the nucleobase-polyamine conjugate ligands may have the potential for enhancement of the cytotoxicities of the AP site..
2. Yukiko Abe, Osamu Nakagawa, Rie Yamaguchi, Shigeki Sasaki, Synthesis and Binding Properties of New Selective Ligands for the Nucleobase Opposite the AP Site, Bioorganic & Medicinal Chemistry, 20, 11, 3470-3479, 2012.06, DNA is continuously damaged by endogenous and exogenous factors such as oxidative stress or DNA alkylating agents. These damaged nucleobases are removed by DNA N-glycosylase and form apurinic/apyrimidinic sites (AP sites) as intermediates in the base excision repair (BER) pathway. AP sites are also representative DNA damages formed by spontaneous hydrolysis. The AP sites block DNA polymerase and a mismatch nucleobase is inserted opposite the AP sites by polymerization to cause acute toxicities and mutations. Thus, AP site specific compounds have attracted much attention for therapeutic and diagnostic purposes. In this study, we have developed nucleobase-polyamine conjugates as the AP site binding ligand by expecting that the nucleobase part would play a role in the specific recognition of the nucleobase opposite the AP site by the Watson-Crick base pair formation and that the polyamine part should contribute to the access of the ligand to the AP site by a non-specific interaction to the DNA phosphate backbone. The nucleobase conjugated with 3,3’-diaminodipropylamine (A-ligand, G-ligand, C-ligand, T-ligand and U-ligand) showed a specific stabilization of the duplex containing the AP site depending on the complementary combination with the nucleobase opposite the AP site; i.e., A-ligand to T, G-ligand to C, C-ligand to G, T- and U-ligand to A. The thermodynamic binding parameters clearly indicated that the specific stabilization is due to specific binding of the ligands to the complementary AP site. These results have suggested that the complementary base pairs of the Watson-Crick type are formed at the AP site..
主要学会発表等
1. 阿部由紀子、中川 治、山口莉慧、佐々木茂貴, 塩基欠損部位における疑似的なワトソンークリック塩基対の形成, 第131年会 日本薬学会, 2011.03.
2. Yukiko Abe, Shigeki Sasaki, Selective stabilization of an abasic site by polyamine-nucleobase conjugates, 2010 International Chemical Congress of Pacific Basin Societies, 2010.12.
3. Yukiko Abe, Shigeki Sasaki, Formation of a Pseudo-Base Pair in an Abasic site in the Duplex DNA, 第37回 国際核酸化学シンポジウム, 2010.11.
学会活動
所属学会名
日本化学会
日本薬学会
学術論文等の審査
年度 外国語雑誌査読論文数 日本語雑誌査読論文数 国際会議録査読論文数 国内会議録査読論文数 合計
2013年度      
研究資金
科学研究費補助金の採択状況(文部科学省、日本学術振興会)
2017年度~2018年度, 若手研究(B), 代表, APサイト修復阻害を基にした抗がん効果増強剤の開発.
2015年度~2016年度, 若手研究(B), 代表, DNA脱塩基部位に対する特異的結合および切断分子の開発.
学内資金・基金等への採択状況
2017年度~2017年度, 出産・育児復帰者支援, 代表, APサイト修復阻害に着目した新規抗がん剤の検討.
2016年度~2016年度, 出産・育児復帰者支援, 代表, APサイト修復阻害を起こす新規結合分子の開発.

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