九州大学 研究者情報
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基本情報 研究活動
貞松 由紀子(さだまつ ゆきこ) データ更新日:2024.04.19

助教 /  医学研究院 基礎医学部門 社会環境医学講座


主な研究テーマ
骨代謝疾患を標的とした骨親和性リガンドの開発
キーワード:骨標的, ビスホスホネート
2020.04.
脱塩基部位を標的としたDNA修復阻害剤の開発
キーワード:脱塩基部位, 塩基除去修復
2015.04~2020.03.
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
2008.04~2014.03.
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. Yukiko S. Abe, Shigeki Sasaki, The adduct formation between the thioguanine-polyamine ligands and DNA with the AP site under UVA irradiated and non-irradiated conditions, Bioorganic & Medicinal Chemistry, 2019.10.
2. Yukiko S. Abe, Shigeki Sasaki, 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..
3. 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, 佐々木 茂貴, 2本鎖DNA脱塩基部位に特異的な結合分子によるDNA切断作用, 日本薬学会第133年会, 2013.03.
2. Yukiko Abe, Osamu Nakagawa, Rie Yamaguchi, 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, Osamu Nakagawa, Rie Yamaguchi, 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
日本法医学会
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)
2019年度~2020年度, 基盤研究(C), 代表, APサイト特異的切断およびアルキル化によるDNA修復阻害剤の開発.
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.

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