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
麻生 真理子(あそう まりこ) データ更新日:2019.06.25

准教授 /  薬学研究院 創薬科学部門 医薬化学


主な研究テーマ
医薬応用をめざした蛋白質の化学修飾
キーワード:蛋白質 化学修飾
2015.04.
アミン反応性核酸の開発
キーワード:核酸、アミン、 リジン残基、部位特異的修飾、核酸と相互作用する蛋白質
2008.04.
安定ラジカルを塩基部に直結した核酸を用いた核酸分子の構造研究
キーワード:核酸、スピンラベル、安定ラジカル、ESR
2000.04~2018.03.
酸化的損傷を受けたDNAの反応性に関する研究
キーワード:DNA 酸化的損傷 蛋白質修飾
1994.10.
ビスホスホネート誘導体の合成と機能研究
キーワード:ビスホスホネート、骨、キャリヤー分子
2010.04.
研究業績
主要原著論文
1. Kazuma Shimoda, Takahiro Mitsuoka, Kenta Ueda, Hiroshi Suemune, Go Hirai, Mariko Aso, Synthesis of dendritic bisphosphonates as bone targeting ligands, Tetrahedron Lett., 59, 4528-4531, 2018.11, A dendritic bisphosphonate carrying three bisphosphonate (BP) units in close proximity was designed as a ligand to conjugate large therapeutic molecules for their bone selective delivery. The Bu3P-catalyzed conjugate addition of nitromethane to vinylidene bisphosphonate was effective to construct a quaternary carbon center carrying BP units. Owing to multivalent interactions, the dendritic bisphosphonate showed considerable affinity for the bone mineral hydroxyapatite even in the presence of a competitor, demonstrating potential as a bone targeting ligand..
2. Yusuke Kimuro, Kazuteru Usui, Satoru Karasawa, Go Hirai, Mariko Aso, 7-Hydroxy-3-methyleneisoindolin-1-one as a new ESIPT-fluorescent probe to monitor aqueous environments, Chemical and Pharmaceutical Bulletin, 65, 8, 796-800, 2017.08, A 7-hydroxy derivative of 3-methyleneisoindolin-1-one 1 was synthesized and its properties as a new fluorophore undergoing excited-state intramolecular proton transfer (ESIPT) were investigated. In alcohols and dimethylsulfoxide, 1 exhibited dual emission at ~380 and ~525−541 nm when excited at ~336 nm, which agreed well with the density functional theory (DFT) and time-dependent (TD)-DFT-calculated emission predictions of 1 and its ESIPT tautomer. In aqueous solutions at near neutral pH, 1 exhibited a broad emission band at ~497 nm, presumably caused by the overlap of emissions from 1 and the excited state phenolate species of 1. In binary mixtures of H2O and EtOH, the wavelength and intensity of fluorescence maxima were dependent on the dielectric constant of the solvent, suggesting that 1 could be applied as a fluorescent probe to monitor aqueous environments..
3. Chiemi Gatanaga, Bo Yang, Yuka Inadomi, Kazuteru Usui, Chiyoe Ota, Tsutomu Katayama, Hiroshi Suemune, Mariko Aso, Site-Specific Turn-On Fluorescent Labeling of DNA-Interacting Protein Using Oligodeoxynucleotides That Modify Lysines To Produce 5,6-Dimethoxy 3-Methyleneisoindolin-1-one, ACS Chem. Biol., DOI: 10.1021/acschembio.6b00090, 11, 8, 2216-2221, 2016.06, We have developed oligodeoxynucleotides (ODNs) that modify primary amines to produce 5,6-dimethoxy 3-methyleneisoindolin-1-one. Compared to the oxygen isosteric fluorophore, 4,5-dimethoxyphthalimide, this methyleneisoindolinone was more stable and exhibited an 85 nm blue-shifted fluorescent emission (λmax at 425 nm) with an intensity comparable to that of the phthalimide. Reaction of the DNA-binding domain of Escherichia coli DnaA protein with an ODN containing its binding sequence efficiently afforded a
modified fluorescent protein at a specific lysine residue in the proximity of the ODN. A full-length DnaA protein was also successfully fluorescently labeled. These results demonstrate the potential utility of the ODNs developed in this study for the fluorescent labeling of DNA-interacting protein at the lysine residue of interest..
4. Bo Yang, Akiko Jinnouchi, Kazuteru Usui, Tsutomu Katayama, Hiroshi Suemune, Mariko Aso, Bioconjugation of oligodeoxynucleotides carrying 1,4-dicarbonyl groups via reductive amination with lysine residues, Bioconjugate Chemistry, DOI.10.1021/acs.bioconjchem.5b00361, 26, 8, 1830-1838, 2015.07, We evaluated the efficacy of bioconjugation of oligodeoxynucleotides (ODNs) containing 1,4-dicarbonyl groups, a C4′-oxidized abasic site (OAS) and a newly designed 2′-methoxy analog, via reductive aminations with lysine residues. Dicarbonyls, aldehyde and ketone at C1- and C4-positions of deoxyribose in the ring-opened form of OAS, allowed their efficient reaction with amines. Kinetic studies indicated that reductive amination of OAScontaining ODNs with a proximal amine on the complementary strand proceeded 10 times
faster than the corresponding reaction of an ODN containing an abasic site with C1-aldehyde. Efficient reductive amination between the DNA-binding domain of Escherichia coli DnaA protein and ODNs carrying OAS in the DnaA-binding sequence proceeded at the lysine residue in proximity to the phosphate group at the 5′-position of the OAS, in contrast to unsuccessful conjugation with abasic site ODNs, even they have similar aldehydes. Theoretical calculation indicated that the C1-aldehyde of OAS was more accessible to the target lysine than that of the abasic site. These results demonstrate the potential utility of cross-linking strategies that use dicarbonyl-containing ODNs for the study of protein-nucleic acid interactions. Conjugation with a lysine-containing peptide that lacked specific affinity for ODN was also successful, further highlighting the advantages of 1,4-dicarbonyls..
5. B. Yang, A. Jinnouchi, H. Suemune, M. Aso, Difluoro-C4’-oxidized Aabsic Site for Efficient Amine Modification in Biological Systems, Org. Lett., 14, 5852-5855, 2012.12.
主要総説, 論評, 解説, 書評, 報告書等
主要学会発表等
1. Mariko Aso, Chiemi Gatanaga, Chiyoe Ota, Go Hirai, Yosuke Taniguchi, Shigeki Sasaki, Synthesis of Oligodeoxynucleotides for Lysine Modifi-cation to Induce Solvatochromic Fluorescent Lactam, The 45rd International Symposium on Nucleic Acids Chemistry, 2018.11.
2. Mariko Aso, 潟永 ちえみ, Bo Yang, 太田 千代枝, Hiroshi Suemune, Oligodeoxynucleotides that modify lysines to produce fluorescent lactam for DNA-interacting potein labeling, The 43rd International Symposium on Nucleic Acids Chemistry, 2016.09.
3. 楊 波, 麻生真理子,末宗 洋, 活性化されたジカルボニル基を持つDNAによる標的分子のアミン修飾反応, 第49回化学関連支部合同九州大会, 2012.06.
学会活動
所属学会名
日本薬学会 医薬化学部会
日本化学会生体機能関連化学部会
日本薬学会
日本化学会
有機合成化学協会
フロンティア生命化学研究会
学協会役員等への就任
2010.01~2011.12, 有機合成化学協会九州山口支部, 幹事.
2011.01~2012.12, 有機合成化学協会九州山口支部, 幹事.
2009.02~2010.01, 日本薬学会九州支部, 会計.
学会大会・会議・シンポジウム等における役割
2012.06.30~2012.06.30, 第49回化学関連支部合同九州大会, 有機化学部会 世話人.
2012.05.18~2011.05.18, 有機合成化学協会九州山口支部50周年記念講演会, 実行委員.
2011.08.27~2011.08.27, 有機合成化学協会九州山口支部主催 若手研究者のためのセミナー, 世話人.
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)
2018年度~2020年度, 基盤研究(C), 代表, ターンオン蛍光を伴う部位特異的リジン修飾、クロスリンク形成と蛋白質研究への応用.
2014年度~2016年度, 基盤研究(C), 代表, 反応性核酸を用いた部位特異的リジン残基ラクタム化による蛋白質への機能導入.
2009年度~2011年度, 基盤研究(C), 代表, ユニークなスピンーレドックス特性を持つラジカル直結型核酸の開発.
2006年度~2007年度, 基盤研究(C), 代表, 核酸のインターナルダイナミクスを鋭敏に捕えるスピンラベル化核酸の開発と応用.
学内資金・基金等への採択状況
2017年度~2017年度, 平成29年度QRプログラム, 代表, 蛋白質機能研究に有用な新規蛍光性、反応性基の開発とその部位特異的導入.

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