高性能分離系の開発では、例えば、キャピラリー電気泳動の一分野である動電クロマトグラフィーが動的な構造分配性を持つことを利用して、極めて高い分離選択性を実現するマルチ分離モードシステムを構築した。また、本研究室で高性能分析法を開発し、生命科学研究へと展開している。例えば、飲酒由来のアセトアルデヒド摂取によるDNA 損傷に関する研究を遂行している。ここでは、個人の発がんリスク指標としても重要と考えられる DNA のアセトアルデヒド付加体形成に着目し、質量分析を基盤とする付加体の超高感度分析法の開発を行っている。
We have successfully developed the high-performance separation systems involving capillary electrophoresis, focused on the dynamic structural partitioning-phase in electrokinetic chromatography. We also develop the new separation methods using capillary electrophoresis and HPLC integrated with sensitivity improvement of MS, fluorometric, optical and electrochemical detections. These technologies are applied to the determination of biomarkers, bioactive molecules in biological samples and endcrine disrupting chemicals in environment samples in the field of life science and clinical chemistry. Especially, the advanced analytical systems based on MS technics developed in our laboratory are applied to highly sensitive determination of DNA adducts from acetaldehyde as cancer risk markers, and contribute to investigation of their involvement in carcinogenesis.
In addition, we also investigate neighboring group effects on oxidation and reduction of disulfide bond based on electrochemical measurements and DFT calculation. It was found that neighboring groups can influence the electronic states of neutral, oxidized, and reduced disulfide bonds significantly. In order to develop a new conductive material and drugs we are currently investigating the role of this effect in biological systems.
研究課題 Research Objectives
高性能キャピラリー電気泳動システムの開発と生命科学研究への応用 Development of highly selective and sensitive capillary electrophoresis systems and their applications in the field of life science
高速液体クロマトグラフィー－質量分析計測システムの生命科学研究、臨床化学研究への応用 Application of a LC-MS system in the fields of life science and clinical chemistry
ジスルフィド基の隣接基効果を利用した低酸化電位を有する機能性分子構築に関する研究 Molecular designs and syntheses of functional molecules with low oxidation potential based on neighboring effects of the disulfide group.
有機電気化学の分子科学への応用：機能性分子創製と分子解析の電気化学 Development of electroorganic chemistry in the field of molecular science: electrochemistry for discovery and molecular analysis of functional molecules
最近の研究成果 Research Results
Matsumoto H., Kawashima N., Yamamoto H., Nakama M., Otsuka H., Ago Y., Sasai H., Kubota K., Ozeki M., Kawamoto N., Esaka Y., Ohnishi H., In vitro functional analysis of four variants of human asparagine synthetase, J. Inher. Metab. Ðis., 44, 1226-1234 (2021).
Esaka Y., Aruga H., Kunishima S., Yamamoto T., Murakami H, Sawama Y., Sajiki H., Uno B., Preparation of N2-Ethyl-2′-deoxyguanosine-d4 as an internal standard for the electrospray ionization-tandem mass spectrometric determination of DNA damage by acetaldehyde, Anal. Sci., 36, 877-880 (2020).
Yamamoto, T., Sakamoto, K., Esaka, Y., Uno B., Highly Sensitive Fluorescence Detection of Daptomycin in Murine Samples through Derivatization with 2,3-Naphthalenedialdehyde, Anal. Sci., 36, 1285-1288 (2020).
Esaka Y., Kunishima S., Aruga H., Yamamoto T., Murakami H, Teshima, N., Uno B., Preparation of Cyclic-1, N2-propano-2′-deoxyguanosine-d7 as an Internal Standard for ESI-MS/MS Determination of DNA Damage from Acetaldehyde, Anal Sci., 35, 1393-1397 (2019).
Esaka Y., Hisato K., Yamamoto T., Murakami H, Uno B., Evaluation of Type-A Endonucleases for the Quantitative Analysis of DNA Damage due to Exposure to Acetaldehyde Using Capillary Electrophoresis, Anal. Sci., 34 (8), 901-906 (2018).
Murakami H., Horiba R., Iwata T., Miki Y., Uno B., Sakai T., Kaneko K., Ishihama Y., Teshima N., Esaka Y., Progress in a Selective Method for the Determination of the Acetaldehyde-derived DNA Adducts by Using HILIC-ESI-MS/MS, Talanta, 177, 12-17 (2018).
