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Synthesis of interigent derivatization reagents and discovery of disease-related biomarkers based on chiral metabolome analysis

Research Project

Project/Area Number 24590055
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Physical pharmacy
Research InstitutionUniversity of Shizuoka

Principal Investigator

TOYO'OKA Toshimasa  静岡県立大学, 薬学部, 教授 (40183496)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords光学活性誘導体化試薬 / キラルメタボロミクス / バイオマーカー探索 / 疾病診断 / 液体クロマトグラフィー / 質量分析 / 質量分析法 / 光学活性アミノ酸 / 光学活性カルボン酸 / 光学活性アミン
Outline of Final Research Achievements

This study deals with the synthesis of new chiral derivatization reagents for the enantiomers of amines and carboxyls in LC-MS/MS analysis and their application to chiral metobolomics.
(S)-PyT-N, PCP2 and DMT-3(S)-Apy were designed and synthesized as the reagents for chiral carboxyls, whereas (R)-PyT-C, DMT-L-Pro-OSu, L-PGA and L-PGA-OSu were developed for chiral amines. L-PGA-d5, an isotopic valiant of L-PGA, was also synthesized to avoid the matrics effect in LC-MS analysis. The precise determination of D/L-amino acids was performed using the light and heavy reagents. Furthermore, DMT-3(S)-Apy was applied for the determination of carboxyls in saliva of diabetic patients. The ratio of D/L-lactic acids in the saliva of diabetic patients was higher than that of healthy persons. This result suggests that the determination of chiral metabolites is efficient for biomarker discovery related for some diseases.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (33 results)

All 2015 2014 2013 2012 Other

All Journal Article (12 results) (of which Peer Reviewed: 12 results,  Acknowledgement Compliant: 4 results,  Open Access: 1 results) Presentation (16 results) (of which Invited: 2 results) Book (2 results) Remarks (3 results)

  • [Journal Article] Profiling of chiral and achiral carboxylic acid metabolomics: Synthesis and evaluation of triazine-type chiral derivatization reagents for carboxylic acids by LC-ESI-MS/MS and the application to saliva of healthy volunteers and diabetic patients2015

    • Author(s)
      Takahiro Takayama, Tomohiro Kuwabara, Toshio Maeda, Ichiro Noge, Yutaka Kitagawa, Koichi Inoue, Kenichiro Todoroki, Jun Zhe Min, Toshimasa Toyo'oka
    • Journal Title

      Analytical and Bioanalytical Chemistry

      Volume: 407 Issue: 3 Pages: 1003-1014

    • DOI

      10.1007/s00216-014-8275-9

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Blood-based diagnosis of Alzheimer's disease using fingerprinting metabolomics based on hydrophilic interaction liquid chromatography with mass spectrometry and multivariate statistical analysis2015

    • Author(s)
      Koichi Inoue, Hirofumi Tsuchiya, Takahiro Takayama, Hiroyasu Akatsu,Yoshio Hashizume, Takayuki Yamamoto, Noriyuki Matsukawa, Toshimasa Toyo'oka
    • Journal Title

      Journal of Chromatography B

      Volume: 974 Pages: 24-34

    • DOI

      10.1016/j.jchromb.2014.10.022

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Isotopic variants of light and heavy L-pyroglutamic acid succinimidyl esters as the derivatization reagents for DL-amino acid chiral metabolomics identification by liquid chromatography and electrospray ionization mass spectrometry2014

    • Author(s)
      Toshiki Mochizuki, Kenichiro Todoroki, Koichi Inoue, Jun Zhe Min, Toshimasa Toyo'oka
    • Journal Title

      Analytica Chimica Acta

      Volume: 811 Pages: 51-59

    • DOI

      10.1016/j.aca.2013.12.016

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Simultaneous determination of post-translational racemization and isomerization of N-terminal amyloid-β in Alzheimer's brain tissues by covalent chiral derivatized ultraperformance liquid chromatography tandem mass spectrometry.2014

    • Author(s)
      Inoue K, Hosaka D, Mochizuki N, Akatsu H, Tsutsumiuchi K, Hashizume Y, Matsukawa N, Yamamoto T, Toyo'oka T.
    • Journal Title

      Anal Chem.

      Volume: 86 Issue: 1 Pages: 797-804

    • DOI

      10.1021/ac403315h

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of a series of prolylamidepyridine as the chiral derivatization reagents for enantioseparation of carboxylic acids by LC-ESI-MS/MS and the application to human saliva2014

    • Author(s)
      Tomohiro Kuwabara, Takahiro Takayama, Kenichiro Todoroki, Koichi Inoue, Jun Zhe Min, Toshimasa Toyo'oka
    • Journal Title

      Analytical and Bioanalytical Chemistry

      Volume: 406 Issue: 11 Pages: 2641-2649

    • DOI

      10.1007/s00216-014-7637-7

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Novel chiral derivatization reagents possessing a pyridyl thiourea structure for enantiospecific determination of amines and carboxylic2013

    • Author(s)
      Nagao R, Tsutsui H, Mochizuki T, Takayama T, Kuwabara T, Min JZ
    • Journal Title

      Journal of Chromatography A

      Volume: 1,296 Pages: 111-118

    • DOI

      10.1016/j.chroma.2013.03.019

    • Related Report
      2013 Research-status Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Relative quantification of enantiomers of chiral amines by high-throughout LC-ESI-MS/MS using isotopic variants of light and heavy L-2013

    • Author(s)
      Mochizuki T, Taniguchi S, Tsutsui H, Min TZ, Inoue K
    • Journal Title

      Analytica Chimica Acta

      Volume: 773 Pages: 76-82

    • DOI

      10.1016/j.aca.2013.02.026

    • Related Report
      2013 Research-status Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] High-throughput LC-MS/MS based simultaneous determination of polyamines including N-acetvlated forms in human saliva and the diagnostic approach2013

    • Author(s)
      Tsutsui H, Mochizuki T, Inoue K, Toyama T. Yoshimoto N. Endo Y.
    • Journal Title

      analytical chemistry

      Volume: 85 Issue: 24 Pages: 11835-11842

    • DOI

      10.1021/ac402526c

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] A novel derivatization reagent possessing a bromoquinolinium structure for biological carboxylic acids in HPLC-ESI-MS/MS2013

    • Author(s)
      Yuko Mochizuki, Shinsuke Inagaki, Jun Zhe Min, Koichi Inoue, Kenichiro Todoroki, Toshimasa Toyo’oka
    • Journal Title

      Journal of Separation Science

      Volume: 36 Issue: 12 Pages: 1883-1889

    • DOI

      10.1002/jssc.201300083

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Metabolic profiling of Alzheimer' s disease brains。2013

    • Author(s)
      Inoue K, Tsutsui H, Akatsu H, Hashizume Y, Matsukawa N, Yamamoto T, Toyo'oka T.
    • Journal Title

      Scientific Reports

      Volume: 3 Issue: 1 Pages: 2-364

    • DOI

      10.1038/srep02364

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Simultaneous determination of DL-lactic acid and DL-3-hydroxybutyric acid enantiomers in saliva of diabetes mellitus patients by high-throughput LC-ESI-MS/MS.2012

    • Author(s)
      Tsutsui H, Mochizuki T, Maeda T, Noge I, Kitagawa Y, Min JZ, Todoroki K, Inoue K, Toyo'oka T.
    • Journal Title

      Analytical and Bioanalytical Chemistry

      Volume: 404 Issue: 6-7 Pages: 1925-1934

    • DOI

      10.1007/s00216-012-6320-0

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Chiral amines as reagents for HPLC-MS enantioseparation of chiral carboxylic acids.2012

    • Author(s)
      Tsutsui H, Fujii S, Sakamoto T, Min JZ, Todoroki K, Toyo'oka T
    • Journal Title

      Journal of Separation Science

      Volume: 35 Issue: 13 Pages: 1551-1559

    • DOI

      10.1002/jssc.201200091

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] ノンターゲットキラルメタボロミクスの測定戦略2014

    • Author(s)
      望月俊樹、高山卓大、井之上浩一、轟木堅一郎、閔 俊哲、豊岡利正
    • Organizer
      第25回クロマトグラフィー科学会議
    • Place of Presentation
      京都
    • Year and Date
      2014-12-11 – 2014-12-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] 光学活性誘導体化試薬light/heavy-DMT-3(S)-Apyを用いた唾液中キラルカルボン酸メタボロミクス2014

    • Author(s)
      高山卓大、前田利男、野毛一郎、北川 裕、轟木堅一郎、井之上浩一、閔 俊哲、豊岡利正
    • Organizer
      日本分析化学会 第63年会
    • Place of Presentation
      広島
    • Year and Date
      2014-09-17 – 2014-09-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] LC-MSによるメタボロミクス測定技術の食品分析・病態解析への適用2014

    • Author(s)
      豊岡利正
    • Organizer
      日本食品科学工学会 第61回大会
    • Place of Presentation
      福岡
    • Year and Date
      2014-08-28 – 2014-08-30
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] UHPLC-MSを用いたアルツハイマー病の標的プロテオミクス/メタボロミクス統合解析2014

    • Author(s)
      山本誠、井之上浩一、赤津裕康、松川則之、橋詰良夫、山本孝之、豊岡利正
    • Organizer
      第27回バイオメディカル分析科学シンポジウム
    • Place of Presentation
      熊本
    • Year and Date
      2014-08-20 – 2014-08-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] キラルメタボロミクスを指向したLC-ESI-MS/MS用新規キラル誘導体化試薬を用いた生体試料中DL-アミノ酸分析2014

    • Author(s)
      望月俊樹、高山卓大、轟木堅一郎、井之上浩一、閔 俊哲、豊岡利正
    • Organizer
      第27回バイオメディカル分析科学シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2014-08-20 – 2014-08-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] 光学活性誘導体化試薬DMT-3(S)-Apyを用いた唾液中カルボン酸メタボロミクスのLC-ESI-MS/MS分析2014

    • Author(s)
      高山卓大、桑原朋大、前田利男、野毛一郎、北川裕、井之上浩一、轟木堅一郎、豊岡利正
    • Organizer
      第27回バイオメディカル分析科学シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2014-08-20 – 2014-08-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] 非侵襲的試料を用いた疾病診断2013

    • Author(s)
      豊岡利正
    • Organizer
      第44回 中部化学関係学協会支部連合秋季大会
    • Place of Presentation
      浜松
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 光学活性カルボキシル化合物のLC-MS/MS分析用光学活性誘導体化試薬の開発および生体試料への応用2013

    • Author(s)
      高山卓大、桑原朋大、閔 俊哲、井之上浩一、轟木堅一郎、豊岡利正
    • Organizer
      第24回クロマトグラフィー科学会議
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] トリアジン構造を有する光学活性誘導体化試薬の開発とLC-MS/MS分析2013

    • Author(s)
      高山卓大、桑原朋大、長尾竜治、閔 俊哲、井之上浩一、轟木堅一郎、豊岡利正
    • Organizer
      日本分析化学会第62年会
    • Place of Presentation
      大阪
    • Related Report
      2013 Research-status Report
  • [Presentation] 光学活性アミン・アミノ酸を標的とした L-Pyroglutamic acid 活性エステル型キラル誘導体化試薬の開発2013

    • Author(s)
      望月俊樹、閔 俊哲、井之上浩一、轟木堅一郎、豊岡利正
    • Organizer
      第26回バイオメディカル分析科学シンポジウム
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] アルツハイマー病脳のLC-MSによるメタボローム解析2013

    • Author(s)
      筒井陽仁、井之上浩一、赤津裕康、橋詰良夫、松川則之、山本孝之、豊岡利正
    • Organizer
      第26回バイオメディカル分析科学シンポジウム
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] LC-MS/MS分析を目的としたカルボン酸標識用キラル誘導体化試薬の開発2013

    • Author(s)
      桑原朋大、森田真介、長尾竜治、閔 俊哲、轟木堅一郎、井之上浩一、豊岡利正
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] 光学活性アミンを標的としたキラル誘導体化試薬の開発とキラルメタボロミクスへの展開2013

    • Author(s)
      望月俊樹、谷口さゆり、筒井陽仁、閔 俊哲、轟木堅一郎、井之上浩一、豊岡利正
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] チオウレア構造を有するLC/ESI-MS/MSキラル誘導体化試薬の開発2012

    • Author(s)
      長尾竜治、閔 俊哲、井之上浩一、轟木堅一郎、豊岡利正
    • Organizer
      第22回クロマトグラフィー科学会議
    • Place of Presentation
      岐阜
    • Related Report
      2012 Research-status Report
  • [Presentation] 光学活性アミンを標的としたLC-MS/MS用キラル誘導体化試薬としてのL-Pyroglutamic acid2012

    • Author(s)
      望月俊樹、谷口さゆり、閔 俊哲、轟木堅一郎、井之上浩一、豊岡利正
    • Organizer
      日本分析化学会第61年会
    • Place of Presentation
      金沢
    • Related Report
      2012 Research-status Report
  • [Presentation] 生体内光学活性カルボン酸の分離分析に応用可能なLC/ESI-MS/MS用誘導体化試薬の開発2012

    • Author(s)
      桑原朋大、森田真介、長尾竜治、閔 俊哲、轟木堅一郎、井之上浩一、豊岡利正
    • Organizer
      日本分析化学会第61年会
    • Place of Presentation
      金沢
    • Related Report
      2012 Research-status Report
  • [Book] Chapter 14, Chiral Benzofurazan-Derived Derivatization Reagents for Indirect Enantioseparations by HPLC. Chiral Separations: Methods and Protocols, 2nd Ed. Methods in Molecular Biology, Vol. 9702013

    • Author(s)
      Toshimasa Toyo'oka
    • Publisher
      Humana Press
    • Related Report
      2013 Research-status Report
  • [Book] Amino Acid Analysis, Methods and Protocols, Methods in Molecular Biology2012

    • Author(s)
      Shinsuke Inagaki, Toshimasa Toyo'oka
    • Publisher
      Humana Press
    • Related Report
      2012 Research-status Report
  • [Remarks] 静岡県立大学薬学部生体機能分子分析学教室

    • URL

      http://w3pharm.u-shizuoka-ken.ac.jp/analchem/

    • Related Report
      2014 Annual Research Report
  • [Remarks] 研究業績

    • URL

      http://w3pharm.u-shizuoka-ken.ac.jp/analchem/achievement.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] 研究室ホームページ

    • URL

      http://w3pharm.u-shizuoka-ken.ac.jp/analchem/

    • Related Report
      2013 Research-status Report

URL: 

Published: 2013-05-31   Modified: 2019-07-29  

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