Development and application of chemical genomic platforms by use of synthetic organic chemistry

• Project/Area Number: 19681023
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Living organism molecular science
• Research Institution: Tohoku University
• Principal Investigator: KANOH Naoki Tohoku University, 大学院・薬学研究科, 准教授 (40317293)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥21,450,000 (Direct Cost: ¥16,500,000、Indirect Cost: ¥4,950,000); Fiscal Year 2009: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2008: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2007: ¥12,610,000 (Direct Cost: ¥9,700,000、Indirect Cost: ¥2,910,000)
• Keywords: マイクロアレイ / 有機化学 / ケミカルゲノミクス / 生物活性物質

Research Abstract

Small-molecule microarray and affinity matrix technologies have been developed. Firstly, by introducing a cleavable site in a photoactivatable linker, which is used to immobilize small molecules on an affinity matrix, validation of the immobilized small molecule on the affinity matrix became possible for the first time. The newly developed cleavable photoactivatable platform also permits the efficient detection of proteins covalently bound to the immobilized small molecule. Secondly, small-molecule microarray platforms that detect substrate specificity of cytochrome P450 have been developed.

Research Products

• [Journal Article] (2010)
  • Author(s): N.Kanoh, H.Takayama, K.Honda, T.Moriya, T.Teruya, S.Simizu, H.Osada, Y.Iwabuchi
  • Journal Title: Bioconjugate Chem. 21 Pages: 182-186
  • Peer Reviewed
• [Journal Article] (2010)
  • Author(s): N. Kanoh, H. Takayama, K. Honda, T. Moriya, T. Teruya, S. Simizu, H. Osada, Y. Iwabuchi
  • Journal Title: Bioconjugate Chemistry 21 Pages: 182-182
  • Peer Reviewed
• [Journal Article] Cleavable linker for photo-cross-linked small-molecule affinity matrix (2010)
  • Author(s): N.Kanoh
  • Journal Title: Bioconjugate Chemistry 21 Pages: 182-186
  • Peer Reviewed
• [Journal Article] Syntheses and Biological Evaluation of Irciniastatin A and the C1-C2 Alkyne Analogue (2010)
  • Author(s): T.Watanabe
  • Journal Title: Organic Letters 12 Pages: 1040-1043
  • Peer Reviewed
• [Journal Article] Structure-activity relationship of C-5-curcuminoids and synthesis of their molecular probes thereof (2010)
  • Author(s): H.Yamakoshi
  • Journal Title: Bioorganic & Medicinal Chemistry 18 Pages: 1083-1092
  • Peer Reviewed
• [Journal Article] Total Synthesis and Determination of the Absolute Configuration of(-)-Idesolide (2010)
  • Author(s): H.Yamakoshi
  • Journal Title: Organic Letters 12 Pages: 980-983
  • Peer Reviewed
• [Journal Article] (2009)
  • Author(s): I.Miyazaki, H.Okumura, S.Simizu, Y.Takahashi, N.Kanoh, Y.Muraoka, Y.Nonomura, H.Osada
  • Journal Title: Chembiochem 10 Pages: 845-852
  • Peer Reviewed
• [Journal Article] (2009)
  • Author(s): I. Miyazaki, H. Okumura, S. Simizu, Y. Takahashi, N. Kanoh, Y. Muraoka, Y. Nonomura, H. Osada
  • Journal Title: Chembiochem 10 Pages: 845-845
  • Peer Reviewed
• [Journal Article] Structure-Affinity Relationship Study of Bleomycins and Shble Protein by Use of a Chemical Array (2009)
  • Author(s): I.Miyazaki
  • Journal Title: ChemBioChem 10 Pages: 845-852
  • Peer Reviewed
• [Journal Article] An Expedient Route to a Potent Gastrin/CCK-B Receptor Antagonist(+)-AG-041R (2009)
  • Author(s): S.Sato
  • Journal Title: Journal of Organic Chemistry 74 Pages: 7522-7524
  • Peer Reviewed
• [Journal Article] Highly enantioselective intramolecular aza-spiroannulation onto indoles using chiral rhodium catalysis : Asymmetric entry to the spiro-beta-lactam core of chartellines (2009)
  • Author(s): S.Sato
  • Journal Title: Chemical Communications Pages: 6264-6266
  • Peer Reviewed
• [Journal Article] Syntheses of naturally occurring cytotoxic[7.7]paracyclophanes, (-)-cylindrocyclophane A and its enantiomer, and implications for biological activity (2009)
  • Author(s): H.Yamakoshi
  • Journal Title: Organic & Bioorganic Chemistry 7 Pages: 3772-3781
  • Peer Reviewed
• [Journal Article] Total synthesis of methyl sarcophytoate, a marine natural biscembra-noid (2009)
  • Author(s): Takahiro Ichige
  • Journal Title: Journal of Organic Chemistry 74 Pages: 230-243
  • Peer Reviewed
• [Journal Article] Synthetic, studies on daphnicyclidin A : Enantiocontrolled construction of the BCD ring system (2009)
  • Author(s): Shuhei Ikeda
  • Journal Title: Organic Letters 11 Pages: 1833-1836
  • Peer Reviewed
• [Journal Article] (2008)
  • Author(s): M.Kawatani, H.Okumura, K.Honda, N.Kanoh, M.Muroi, N.Dohmae, M.Takami, M.Kitagawa, Y.Futamura, M.Imoto, H.Osada
  • Journal Title: Proc.Natl.Acad.Sci.U.S.A. 105 Pages: 11691-11696
  • Peer Reviewed
• [Journal Article] (2008)
  • Author(s): N.Kanoh, T.Nakamura, K.Honda, H.Yamakoshi, Y.Iwabuchi, H.Osada
  • Journal Title: Tetrahedron 64 Pages: 5692-5698
  • Peer Reviewed
• [Journal Article] (2008)
  • Author(s): M. Kawatani, H. Okumura, K. Honda, N. Kanoh, M. Muroi, N. Dohmae, M. Takami, M. Kitagawa, Y. Futamura, M. Imoto, H. Osada
  • Journal Title: P Natl Acad Sci USA 105 Pages: 11691-11691
  • Peer Reviewed
• [Journal Article] (2008)
  • Author(s): N. Kanoh, T. Nakamura, K. Honda, H. Yamakoshi, Y. Iwabuchi, H. Osada
  • Journal Title: Tetrahedron 64 Pages: 5692-5692
  • Peer Reviewed
• [Journal Article] Efficient entry to the pyrroloquinoline core of martinella alkaloids vianovel base-catalyzed Mukaiyama-Mannich reaction (2008)
  • Author(s): Shuhei Ikeda
  • Journal Title: Chemistry Letters 37 Pages: 962-963
  • Peer Reviewed
• [Journal Article] Distribution of phto-cross-linked products from 3-ary-3-trifluoromethyl-diazirines and alcohols (2008)
  • Author(s): Naoki Kanoh
  • Journal Title: Tetrahedron 64 Pages: 5692-5698
  • Peer Reviewed
• [Journal Article] Synthesis and biological activities of reveromycin A and spirofungin A derivatives (2008)
  • Author(s): Tadashi Shimizu
  • Journal Title: Bioorganic & Medicinal Chemistry Letters 18 Pages: 3756-3760
  • Peer Reviewed
• [Journal Article] Total Synthesis of Methyl Sarcophytoate (2007)
  • Author(s): Takahiro Ichige
  • Journal Title: Journal of the American Chemical Society 129 Pages: 9862-9863
  • Peer Reviewed
• [Journal Article] Synthesis of an Enantiomeric DNA Oligomer and Its T-Hg (II)-T Base-Pair Formation (2007)
  • Author(s): Kaichiro Haruta
  • Journal Title: Nucleic Acids Symposium Series Pages: 187-188
  • Peer Reviewed
• [Presentation] 特異的切断サイトを有する新規光親和型小分子アフィニティービーズの開発 (2010)
  • Author(s): 守谷崇
  • Organizer: 日本化学会第130年会
  • Place of Presentation: 岡山
  • Year and Date: 2010-03-29
• [Presentation] 抗腫瘍活性天然物ビセニスタチンの合成と構造活性相関 (2010)
  • Author(s): 中村織依菜
  • Organizer: 日本化学会第130年会
  • Place of Presentation: 岡山
  • Year and Date: 2010-03-28
• [Presentation] 有機分子触媒を用いた分子内不斉アルドール反応によるキラルビシクロ環構築法の開発研究 (2010)
  • Author(s): 村崎広太
  • Organizer: 日本化学会第130年会
  • Place of Presentation: 岡山
  • Year and Date: 2010-03-28
• [Presentation] 8-オキサビシクロ[3.2.1]型キラル合成素子の開発研究 (2010)
  • Author(s): 川住宗生
  • Organizer: 日本化学会第130年会
  • Place of Presentation: 岡山
  • Year and Date: 2010-03-28
• [Presentation] 蛋白質-小分子リガンド間相互作用検出のための有機化学 (2009)
  • Author(s): 叶直樹
  • Organizer: 有機合成化学協会東北支部青森地区講演会
  • Place of Presentation: 弘前
  • Year and Date: 2009-12-11
• [Presentation] 有機合成化学を基盤とした天然有機化合物のケミカルバイオロジー (2009)
  • Author(s): 叶直樹
  • Organizer: 第3回万有財団若手交流セミナー
  • Place of Presentation: 唐津ビューホテル
  • Year and Date: 2009-11-22
• [Presentation] 有機合成化学を基盤とした天然有機化合物のケミカルバイオロジー (2009)
  • Author(s): 叶直樹
  • Organizer: 第3回万有財団若手交流セミナー
  • Place of Presentation: 唐津
  • Year and Date: 2009-11-22
• [Presentation] 構造活性相関を志向した抗腫瘍活性天然物ビセニスタチンの合成研究 (2009)
  • Author(s): 福田隼
  • Organizer: 第35回 反応と合成の進歩シンポジウム
  • Place of Presentation: 金沢
  • Year and Date: 2009-11-17
• [Presentation] 抗腫瘍性マクロライドFD-891の合成研究 (2009)
  • Author(s): 宮崎雄太
  • Organizer: 第48回日本薬学会東北支部大会
  • Place of Presentation: 仙台
  • Year and Date: 2009-10-18
• [Presentation] 8-オキシビシクロ[3.2.1]型キラル合成素子の開発研究 (2009)
  • Author(s): 川住宗生
  • Organizer: 第48回日本薬学会東北支部大会
  • Place of Presentation: 仙台
  • Year and Date: 2009-10-18
• [Presentation] 有機分子触媒を用いた分子内アルドール反応によるキラルビシクロ環構築法の開発研究 (2009)
  • Author(s): 村崎広太
  • Organizer: 第48回日本薬学会東北支部大会
  • Place of Presentation: 仙台
  • Year and Date: 2009-10-18
• [Presentation] 抗腫瘍活性食用植物成分 curcumin をリードとする創薬化学研究 (2009)
  • Author(s): 山越博幸
  • Organizer: 第48回日本薬学会東北支部大会
  • Place of Presentation: 仙台
  • Year and Date: 2009-10-18
• [Presentation] 抗腫瘍活性天然物(+)-irciniastatin A/psymberin の全合成 (2009)
  • Author(s): 渡辺翼
  • Organizer: 第51回天然有機化合物討論会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-10-09
• [Presentation] タンパク質-小分子リガンド間相互作用検出のための有機化学 (2009)
  • Author(s): 叶直樹
  • Organizer: 化学系学術協会東北大会平成
  • Place of Presentation: 日本大学工学部
  • Year and Date: 2009-09-20
• [Presentation] 蛋白質-小分子リガンド間相互作用検出のための有機化学 (2009)
  • Author(s): 叶直樹
  • Organizer: 化学系学術協会東北大会
  • Place of Presentation: 郡山
  • Year and Date: 2009-09-20
• [Presentation] 有機合成化学を基盤とした天然有機化合物のケミカルバイオロジー (2009)
  • Author(s): 叶直樹
  • Organizer: 第26回 有機合成化学セミナー
  • Place of Presentation: 前橋
  • Year and Date: 2009-09-16
• [Presentation] Development of Photo-Cross-Linked Small-Molecule Microarrays and Affinity Matrix as Chemical Genetic Screening Platforms (2009)
  • Author(s): N.Kanoh
  • Organizer: CSI Singapore, NUS, and Tohoku University G-COE Loint Symposium
  • Place of Presentation: Genome Institute of Singapore
  • Year and Date: 2009-09-09
• [Presentation] Development of Photo-Cross-Linked Small-Molecule Microarray and Affinity Matrix as Chemical Genetic Screening Platforms (2009)
  • Author(s): N.Kanoh
  • Organizer: CSI Singapore, NUS-Tohoku University GCOE Joint Symposium
  • Place of Presentation: Genome Institute of Singapore, Sigapore
  • Year and Date: 2009-09-09
• [Presentation] リガンド反応性分子標的を検出・同定する開裂型 photoaffinity beads (2009)
  • Author(s): 高山浩
  • Organizer: 仙台万有シンポジウム
  • Place of Presentation: 仙台
  • Year and Date: 2009-06-13
• [Presentation] 有機合成化学を基板とした天然有機化合物のケミカルバイオロジー (2009)
  • Author(s): 叶直樹
  • Organizer: 新規素材探索研究会第8回セミナー
  • Place of Presentation: 新横浜富士ビューホテル
  • Year and Date: 2009-06-05
• [Presentation] 有機合成化学を基板とした天然有機化合物のケミカルバイオロジー (2009)
  • Author(s): 叶直樹
  • Organizer: 新規素材探索研究会第8回セミナー
  • Place of Presentation: 新横浜
  • Year and Date: 2009-06-05
• [Presentation] 低分子化合物のターゲット探索に用いる開裂型photoaffinity beadsの開発 (2009)
  • Author(s): 高山浩、叶直樹、本田香織、守谷崇、照屋貴之、清水史郎、長田裕之、岩渕好治
  • Organizer: 日本ケミカルバイオロジー学会第4回年会
  • Place of Presentation: 神戸市産業振興センター
  • Year and Date: 2009-05-18
• [Presentation] 低分子化合物のターゲット探索に用いる開裂型 photoaffinity beads の開発 (2009)
  • Author(s): 高山浩
  • Organizer: 日本ケミカルバイオロジー学会第4回年会
  • Place of Presentation: 神戸
  • Year and Date: 2009-05-18
• [Presentation] KSRP特異的リガンドGO-Y086 (2009)
  • Author(s): 叶直樹
  • Organizer: 日本ケミカルバイオロジー学会第4回年会
  • Place of Presentation: 神戸
  • Year and Date: 2009-05-18
• [Presentation] Cytochrome P450による基質構造変化を検出する化合物アレイ型プラットフォームの開発 (2009)
  • Author(s): 高山浩
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 京都国際会議場、京都
  • Year and Date: 2009-03-27
• [Presentation] Chemosite non-selective organic reaction in natural product-based chemical genetics (2008)
  • Author(s): N.Kanoh
  • Organizer: 8^<th> Tateshina Conference on Organic Chemistry
  • Place of Presentation: 蓼科フォーラム
  • Year and Date: 2008-11-07
• [Presentation] 有機合成化学を基盤とした天然有機化合物のケミカルバイオロジー (2008)
  • Author(s): 叶直樹
  • Organizer: 第26回有機合成化学セミナー
  • Place of Presentation: 前橋市中央公民館
  • Year and Date: 2008-09-16
• [Presentation] Photo-generated carbene as a chemical handle for functionalizing small molecules (2008)
  • Author(s): Naoki Kanoh
  • Organizer: IUPAC International Conference on Biodiversity and Natural Products ICOB-6 & ISCNP-26
  • Place of Presentation: Delta Prince Edward, Charlottetown, PEI, Canada
  • Year and Date: 2008-07-15
• [Presentation] Photo-generated carbene as a possible universal chemical handle for functionalizing small molecules (2008)
  • Author(s): N.Kanoh
  • Organizer: IUPAC International Conference on Biodiversity and Natural Products ICOB-6 & ISCNP-26
  • Place of Presentation: Prince Edward Island, Canada
  • Year and Date: 2008-07-05
• [Presentation] 酸化酵素cytochrome P450の基質と阻害剤を検出する化合物アレイ型プラットフォームの開発 (2008)
  • Author(s): 叶直樹
  • Organizer: 日本ケミカルバイオロジー研究会第3回年会
  • Place of Presentation: 学術総合センター、東京
  • Year and Date: 2008-05-19
• [Presentation] Photo-generated carbene as a possible universal chemical handle for functionalizing small molecules (2008)
  • Author(s): Naoki Kanoh
  • Organizer: The 12th Japan-Korea Joint Symposium on Drug Design and Development
  • Place of Presentation: 仙台市戦災復興記念館
  • Year and Date: 2008-05-15
• [Presentation] 生理活性物質の固相単体への官能基非選択的導入法は化学遺伝学研究のパラダイムシフトとなり得るか? (2008)
  • Author(s): 叶 直樹
  • Organizer: 日本薬学会第128年会一般シンポジウム
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市)
  • Year and Date: 2008-03-28
• [Presentation] SPRイメージング法を用いたp38 MAP kinaseとp62の結合部位の同定 (2008)
  • Author(s): 齊藤 安貴子
  • Organizer: 日本農芸化学会2008年度大会
  • Place of Presentation: 名城大学天白キャンパス(愛知県名古屋市)
  • Year and Date: 2008-03-27
• [Presentation] 生理活性物質の固相単体への官能基非選択的導入法は化学遺伝学研究のパラダイムシフトとなり得るか? (2008)
  • Author(s): 叶 直樹
  • Organizer: 第4回理研ケミカルバイオロジーシンポジウム
  • Place of Presentation: 熱海金城館(静岡県熱海市)
  • Year and Date: 2008-02-07
• [Presentation] Chemosite Non-selective Organic Reaction in Natural Product-Based Chemical Genetics (2008)
  • Author(s): Naoki Kanoh
  • Organizer: 8^<th> Tateshina conference on Organic Chemistry
  • Place of Presentation: 蓼科フォーラム、長野県茅野市
• [Presentation] The identification of a novel inhibitor of osteoclastogenesis that acts via inhibition of glyoxalase I (2007)
  • Author(s): 川谷 誠
  • Organizer: AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics
  • Place of Presentation: Moscone Convention Center West, San Francisco, CA
  • Year and Date: 2007-10-22
• [Presentation] Development of A Photo-Cross-Linked Natural Product Microarray Platform for Screening Lysate of Human Cells (2007)
  • Author(s): 宮崎 功
  • Organizer: The 2nd International Workshop on Approaches to Single-Cell Analysis
  • Place of Presentation: 早稲田大学早稲田キャンパス(東京都新宿区)
  • Year and Date: 2007-09-06
• [Presentation] 蛋白質-低分子間相互作用検出法の開発 (2007)
  • Author(s): 叶 直樹
  • Organizer: 日本薬学会東北支部学術講演会
  • Place of Presentation: 東北薬科大学(宮城県仙台市)
  • Year and Date: 2007-05-19
• [Presentation] 低分子リガンドの網羅的スクリーニングを目指したSPRイメージングの高感度化 (2007)
  • Author(s): 高山 浩
  • Organizer: 第2回ケミカルバイオロジー研究会年会
  • Place of Presentation: 京都大学時計台記念(京都府京都市)
  • Year and Date: 2007-05-10
• [Book] Small Molecule Microarrays : Methods and Protocols(M.Uttamchandani, S.Q.Yao, Eds) (2010)
  • Author(s): N.Kanoh
  • Publisher: Humana Press
• [Book] バイオチップ実用化ハンドブック(金子周一、堀池靖浩 監修) (2010)
  • Author(s): 叶直樹
  • Publisher: NTS Inc.
• [Book] Small Molecule Microarrays: Methods and Protocols (2010)
  • Author(s): N. Kanoh
  • Publisher: Humana Press(in press)
• [Book] バイオチップ実用化ハンドブック (2010)
  • Author(s): 叶直樹
  • Publisher: 株式会社エヌ・ティー・エス(印刷中)
• [Book] Small Molecule Microarrays : Methods and Protocols (2010)
  • Author(s): N.Kanoh
  • Publisher: Humana Press(印刷中)
• [Book] Protein Targeting with Small Molecules : Chemical Biology Techniques and Applications(H.Osada, Ed.) (2009)
  • Author(s): N.Kanoh, H.Osada
  • Publisher: Wiley
• [Book] Protein Targeting with Small Molecules: Chemical BIology Techniques and Applications (2009)
  • Author(s): N. Kanoh, H. Osada
  • Total Pages: 57
  • Publisher: Wiley
• [Book] Protein Targeting with Small Molecules : Chemical Biology Techniques and Applications (2009)
  • Author(s): N.Kanoh
  • Publisher: John Wiley & Sons, Inc.
• [Book] ナノバイオ計測の実際(三原久和、小畠英理、馬場嘉信 編) (2007)
  • Author(s): 叶直樹
  • Publisher: 講談社サイエンティフィク
• [Book] マイクロアレイ・バイオチップの最新技術(伊藤嘉浩 監修) (2007)
  • Author(s): 清水史郎、宮崎功、近藤恭光、叶直樹、長田裕之
  • Publisher: CMC Press
• [Book] 分子間相互作用解析ハンドブック(礒辺俊明、中山敬一、伊藤隆司 編) (2007)
  • Author(s): 齋藤亜貴子、叶直樹、長田裕之
  • Publisher: 羊土社
• [Book] マイクロアレイ・バイオチップの最新技術 (2007)
  • Author(s): 清水史郎
  • Total Pages: 305
  • Publisher: シーエムシー出版
• [Book] 分子間相互作用解析ハンドブック(光親和型低分子マイクロアレイを用いた低分子-蛋白質相互作用の検出) (2007)
  • Author(s): 齊藤 安貴子
  • Total Pages: 287
  • Publisher: (株)羊土社
• [Remarks] ホームページ等