Synthesis and analysis of telomere quadruplex DNA-binding porphyrins based on an electrostatic interaction model

• Project/Area Number: 21590118
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Drug development chemistry
• Research Institution: University of Shizuoka
• Principal Investigator: ISHIKAWA Yoshinobu 静岡県立大学, 薬学部, 准教授 (00305004)
• Co-Investigator(Kenkyū-buntansha): YOKOYAMA Hideshi 静岡県立大学, 薬学部, 講師 (70433208)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2010: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: テロメア / テロメラーゼ / 核酸 / 四重鎖 / ポルフィリン / 分子認識 / インシリコ創薬 / 薬学 / 生物物理 / 有機化学

Research Abstract

Drug design, molecular docking, molecular dynamics simulation and synthesis of octacationic porphyrins bearing pyridiniums at their meso and terminal positions were carried out, because these were expected to interact with telomere quadruplex DNA more electrostatically and tightly than did tetracationic porphyrins. In addition, crystallization of the complex of telomere quadruplex DNA with the octacationic porphyrins was attempted.

Research Products

• [Journal Article] Binding mode prediction and inhibitor design of anti-influenza virus diketo acids targeting metalloenzyme RNA polymerase by molecular docking (2011)
  • Author(s): Ishikawa Y. & Fujii S.
  • Journal Title: Bioinformation Volume: 6 Pages: 221-225
  • Peer Reviewed
• [Journal Article] ortho-Selective Nucleophilic Addition of Primary Amines to Silylbenzynes : Synthesis of 2-Silylanilines (2011)
  • Author(s): Ikawa T., Nishiyama T., Shigeta T., Mohri S., Morita S., Takayanagi S., Terauchi Y., Morikawa Y., Takagi A., Ishikawa Y., Fujii S., Kita Y. Akai S.
  • Journal Title: Angew. Chem. Int. Ed. Volume: 50 Pages: 5674-5677
  • Peer Reviewed
• [Journal Article] Novel structure of an N-terminal domain that is crucial for the dimeric assembly and DNA-binding of an archaeal DNA polymerase D large subunit from Pyrococcus horikoshii (2011)
  • Author(s): Matsui I., Urushibata Y., Shen Y., Matsui E., Yokoyama H.
  • Journal Title: FEBS Lett. Volume: 585 Pages: 452-458
  • Peer Reviewed
• [Journal Article] Ortho-selective nucleophilicaddition of primary amines tosilylbenzynes: Synthesis of 2-silylanilines (2011)
  • Author(s): Y . Kita et al.
  • Journal Title: Angew . Chem., Int. Ed. Volume: 50 Issue: 25 Pages: 5674-5677
  • DOI: 10.1002/anie.201100360
  • Peer Reviewed
• [Journal Article] 1, 1', 1'', 1'''-[Porphyrin-5, 10, 15, 20-tetrayltetrakis(3, 1-phenylenemethylene)] tetraquinolinium Tetrabromide (2010)
  • Author(s): Ishikawa Y., Yamashita T., Fujii S., Uno T.
  • Journal Title: Molbank Volume: 704
  • Peer Reviewed
• [Journal Article] Binding of sulphatide to recombinant haemagglutinin of influenza A virus produced by a baculovirus protein expression system (2010)
  • Author(s): Takahashi, T., Satoh, H., Takaguchi, M., Takafuji, S., Yokoyama, H., Fujii, S. & Suzuki, T.
  • Journal Title: J. Biochem Volume: 147 Pages: 459-462
  • NAID: 10027874834
  • Peer Reviewed
• [Journal Article] 膜タンパク質ストマチンの三次元構造とその特異的切断プロテアーゼの機能 (2010)
  • Author(s): 横山英志
  • Journal Title: YAKUGAKU ZASSHI Volume: 130 Pages: 1289-1293
  • NAID: 130000451671
  • Peer Reviewed
• [Journal Article] 1,1',1',1'-[Porphyrin-5,10,15,20-tetrayltetrakis(3,1-phenylenemethylene)]tetraquinolinium Tetrabromide (2010)
  • Author(s): Ishikawa Y., Yamashita T., Fujii S., Uno T.
  • Journal Title: Molbank
  • Peer Reviewed
• [Journal Article] Binding of sulphatide to recombinant haemagglutinin of influenza A virus produced by a baculovirus protein expression system (2010)
  • Author(s): Takahashi, T., Satoh, H., Takaguchi, M., Takafuji, S., Yokoyama, H., Fujii, S., Suzuki, T
  • Journal Title: J.Biochem. Volume: 147 Pages: 459-462
  • NAID: 10027874834
  • Peer Reviewed
• [Journal Article] Zinc(II)-5, 10, 15, 20-tetrakis(a-pyridino-m-tolyl) p orphyrin Tetrabromide (2009)
  • Author(s): Ishikawa Y., Yamashita T., Fujii S., Uno T.
  • Journal Title: Molbank Volume: 637
  • Peer Reviewed
• [Journal Article] Unusual thermal disassembly of the SPFH domain oligomer from Pyrococcus horikoshii (2009)
  • Author(s): Kuwahara, Y., Unzai, S., Nagata, T., Hiroaki, Y., Yokoyama, H., Matsui, I., Ikegami, T., Fujiyoshi, Y. & Hiroaki, H.
  • Journal Title: Biophys. J. Volume: 97 Pages: 2034-2043
  • Peer Reviewed
• [Journal Article] Zinc(II)-5, 10, 15, 20-tetrakis(a-pyridino-m-tolyl)porphyrin Tetrabromide (2009)
  • Author(s): Ishikawa Y., Yamashita T., Fujii S., Uno T.
  • Journal Title: Molbank
  • Peer Reviewed
• [Journal Article] Unusual thermal disassembly of the SPFH domain oligomer from Pyrococcus horikoshii (2009)
  • Author(s): Kuwahara, Y., Unzai, S., Nagata, T., Hiroaki, Y., Yokoyama, H., Matsui, I., Ikegami, T., Fujiyoshi, Y., Hiroaki, H.
  • Journal Title: Biophys.J 97 Pages: 2034-2043
  • Peer Reviewed
• [Presentation] D-ファミリーDNAポリメラーゼの大サブユニットN-末端領域に保存される両親媒性は酵素安定性とDNA合成活性を支配する (2011)
  • Author(s): 松井郁夫、漆畑祐司、申玉龍、松井えり子、横山英志
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-15
• [Presentation] Eg5モータードメイン-阻害剤複合体の調製と結晶化 (2011)
  • Author(s): 加藤詩織、横山英志、澤田潤一、浅井章良、藤井敏
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2011-09-22
• [Presentation] Sulfatideによるインフルエンザウイルスの複製制御 (2011)
  • Author(s): 高橋忠伸、木村愛弓、紅林佑希、高橋俊策、佐藤紘彰、川岸佐和子、横山英志、藤井敏、本家孝一、鈴木康夫、鈴木隆
  • Organizer: 第53回日本脂質生化学会
  • Place of Presentation: 東京
  • Year and Date: 2011-05-13
• [Presentation] Binding mode prediction and design of diketo acid derivatives inhibiting Influenza Viral Metalloenzyme RNA Polymerase (2011)
  • Author(s): Yoshinobu Ishikawa and Satoshi Fujii
  • Place of Presentation: Cambridge, UK
• [Presentation] Molecular mechanism of metal selective uptake by neutrophil-activating protein (2011)
  • Author(s): Osamu Tsuruta, Hideshi Yokoyama, Satoshi Fujii
  • Organizer: The 22nd Congress of the International Union of Crystallography
  • Place of Presentation: Madrid, Spain
• [Presentation] Crystal structures of lipid-raft protein stomatin and its specific protease (2011)
  • Author(s): Hideshi Yokoyama, Satoshi Fujii and Ikuo Matsui
  • Organizer: The 22nd Congress of the International Union of Crystallography
  • Place of Presentation: Madrid, Spain
• [Presentation] The amphipathic nature of the N-terminus conserved in archaeal D-family DNA polymerase large subunit : a potential target for the DNA replication control of archaea (2011)
  • Author(s): Ikuo Matsui, Yuji Urushibata, Yulong Shen, Eriko Matsui, Hideshi Yokoyama
  • Organizer: The 11th International Conference on Thermophiles 2011
  • Place of Presentation: Montana, USA
• [Presentation] Binding mode prediction and design of diketo acid derivatives in hibiting Influenza Viral Metalloenzyme RNA Polymerase (2011)
  • Author(s): Yoshinobu Ishikawa, Satoshi Fujii
  • Organizer: 16th SCI-RSC Cambridge Medicinal Chemistry Symposium
  • Place of Presentation: Cambridge, UK
• [Presentation] Binding of sulfatide to recombinant hemagglutinin of influenza A virus produced by a baculovirus protein expression system (2010)
  • Author(s): Takashi Suzuki, Tadanobu Takahashi, Hiroaki Satoh, Masahiro Takaguchi, Suguru Takafuji, Hideshi Yokoyama, Satoshi Fujii
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-07
• [Presentation] 超好熱菌Pyrococcus horikoshiiのSPFHスーパーファミリーに属する膜タンパク質群の機能構造と膜小胞体形成 (2010)
  • Author(s): 松井郁夫、桑原陽太、松井えり子、廣明秀一、横山英志
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-07
• [Presentation] Binding mode prediction and rational design of diketo acid derivatives targeting metalloenzyme RNA polymerase of influenza virus (2010)
  • Author(s): Yoshinobu Ishikawa, Satoshi Fujii
  • Organizer: 第38回構造活性相関シンポジウム
  • Place of Presentation: 徳島
  • Year and Date: 2010-10-31
• [Presentation] Binding of sulfatide to recombinant hemagglutinin of influenza A virus produced by a baculovirus protein expression system (2010)
  • Author(s): Tadanobu Takahashi, Hiroaki Satoh, Masahiro Takaguchi, Suguru Takafuji, Hideshi Yokoyama, Satoshi Fujii, Takashi Suzuki
  • Organizer: 3rd International Conference on Health and Longevity Sciences
  • Place of Presentation: Shizuoka
  • Year and Date: 2010-10-01
• [Presentation] X-ray crystal structure and function of 1510-N protease specific for stomatin from P. horikoshii (2010)
  • Author(s): Hideshi Yokoyama
  • Organizer: JST-CNRS Joint Seminar 2010
  • Place of Presentation: Paris
  • Year and Date: 2010-09-22
• [Presentation] X-ray crystal structure and function of 1510-N protease specific for stomatin from P.horikoshii (2010)
  • Author(s): Hideshi Yokoyama
  • Organizer: JST-CNRS Joint Seminar 2010
  • Place of Presentation: Paris, France
  • Year and Date: 2010-09-22
• [Presentation] Structure-based Drug Design of Diketo Acid Derivatives inhibiting Influenza Viral Metalloenzyme RNA Polymerase (2010)
  • Author(s): Yoshinobu Ishikawa, Satoshi Fujii
  • Organizer: International Symposium of Medicinal Chemistry
  • Place of Presentation: Brussels, Belgium
  • Year and Date: 2010-09-08
• [Presentation] バキュロウイルス-タンパク質発現システムにより作製したH5型HAのsulfatideへの結合性 (2010)
  • Author(s): 高橋忠伸、佐藤紘彰、高口仁宏、高藤俊、横山英志、藤井敏、鈴木隆
  • Organizer: 第24回インフルエンザ研究者交流の会
  • Place of Presentation: 軽井沢
  • Year and Date: 2010-07-04
• [Presentation] バキュロウイルスータンパク質発現システムにより作製したH5型HAのsulfatideへの結合性 (2010)
  • Author(s): 高橋忠伸、佐藤紘彰、高口仁宏、高藤俊、横山英志、藤井敏、鈴木隆
  • Organizer: 第24回インフルエンザ研究者交流の会
  • Place of Presentation: 軽井沢
  • Year and Date: 2010-07-04
• [Presentation] インフルエンザウィルスの金属酵素RNAポリメラーゼに対するジケト酸誘導体の分子ドッキング (2010)
  • Author(s): 石川吉伸、藤井敏
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
  • Year and Date: 2010-03-29
• [Presentation] 膜タンパク質ストマチンの三次元構造とその特異的切断プロテアーゼの機能 (2010)
  • Author(s): 横山英志、藤井敏、松井郁夫
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
  • Year and Date: 2010-03-29
• [Presentation] インフルエンザウィルスの金属酵素RNAポリメラーゼに対するジケト酸誘導体の分子ドッキング (2010)
  • Author(s): 石川吉伸, 藤井敏
  • Organizer: 日本薬学会 第130年会(岡山)
  • Place of Presentation: 岡山大学
  • Year and Date: 2010-03-29
• [Presentation] 膜タンパク質ストマチンの三次元構造とその特異的切断プロテアーゼの機能 (2010)
  • Author(s): 横山英志, 藤井敏, 松井郁夫
  • Organizer: 日本薬学会 第130年会(岡山)
  • Place of Presentation: 岡山大学
  • Year and Date: 2010-03-29
• [Presentation] ヘリコバクターピロリ好中球活性化タンパク質による金属イオンの貯蔵・放出の構造基盤 (2010)
  • Author(s): 鶴田修、赤尾直也、横山英志、藤井敏
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
  • Year and Date: 2010-03-28
• [Presentation] ヘリコバクターピロリ好中球活性化タンパク質による金属イオンの貯蔵・放出の構造基盤 (2010)
  • Author(s): 鶴田修, 赤尾直也, 横山英志, 藤井敏
  • Organizer: 日本薬学会 第130年会(岡山)
  • Place of Presentation: 岡山大学
  • Year and Date: 2010-03-28
• [Presentation] Binding of sulfatide to recombinant hemagglutinin of influenza A virus produced by a baculovirus protein expression system (2010)
  • Author(s): Tadanobu Takahashi, Hiroaki Satoh, Masahiro Takaguchi, Suguru Takafuji, Hideshi Yokoyama, Satoshi Fujii, Takashi Suzuki
  • Organizer: International Carbohydrate Symposium
  • Place of Presentation: Tokyo
• [Presentation] The structure basis of SPFH proteins linking to vesicle formation from a hyperthermophilic archaeon Pyrococcus horikoshii (2010)
  • Author(s): Ikuo Matsui, Yohta Kuwahara, Eriko Matsui, Hidekazu Hiroaki, Hideshi Yokoyama
  • Organizer: 8th International Congress on Extremophiles
  • Place of Presentation: Azores, Portugal
• [Presentation] The structure basis of SPFH proteins linking to vesicle formation from a hyperthermophilic archaeon Pyrococcus horikoshii (2010)
  • Author(s): Ikuo Matsui, Yohta Kuwahara, Eriko Matsui, Hidekazu Hiroaki, Hideshi Yokoyama
  • Organizer: 8^<th> International Congress on Extremophiles
  • Place of Presentation: Azores, Portugal
• [Presentation] トリインフルエンザウイルスH5型ヘマグルチニンのバキュロウイルスを用いた大量産生系の確立 (2009)
  • Author(s): 佐藤紘彰、高橋忠伸、横山英志、藤井敏、鈴木隆
  • Organizer: 日本病院薬剤師会東海ブロック・日本薬学会東海支部合同学術大会2009
  • Place of Presentation: 四日市
  • Year and Date: 2009-11-23
• [Presentation] X-ray crystal structure of stomatin from P. horikoshii (2009)
  • Author(s): Hideshi Yokoyama
  • Organizer: JST-CNRS Joint Seminar 2009
  • Place of Presentation: つくば
  • Year and Date: 2009-10-30
• [Presentation] X-ray crystal structure of stomatin from P.horikoshii (2009)
  • Author(s): 横山英志
  • Organizer: JST-CNRS Joint Seminar 2009
  • Place of Presentation: Tsukuba
  • Year and Date: 2009-10-30
• [Presentation] Novel crystal structure of Helicobacter pylori neutrophil-activating protein(HP-NAP) (2009)
  • Author(s): Osamu Tsuruta, Naoya Akao, Hideshi Yokoyama, Satoshi Fujii
  • Organizer: Joint Conference of the Asian Crystallographic Association and Chinese Crystallography Society
  • Place of Presentation: 北京
  • Year and Date: 2009-10-24
• [Presentation] 膜タンパク質ストマチンの特異的切断プロテアーゼの二量体構造 (2009)
  • Author(s): 横山英志
  • Organizer: 静岡県立大学2008 USフォーラム
  • Place of Presentation: 静岡
  • Year and Date: 2009-08-05
• [Presentation] 膜タンパク質ストマチンの特異的切断プロテアーゼの二量体構造 (2009)
  • Author(s): 横山英志
  • Organizer: 静岡県立大学 2008USフォーラム
  • Place of Presentation: 静岡県立大学
  • Year and Date: 2009-08-05
• [Presentation] テロメア四重鎖DNAを標的とするカチオン性ポルフィリンの抗腫瘍細胞増殖能 (2009)
  • Author(s): 石川吉伸
  • Organizer: 静岡県立大学2008 USフォーラム
  • Place of Presentation: 静岡
  • Year and Date: 2009-08-04
• [Presentation] テロメア四重鎖DNAを標的とするカチオン性ポルフィリンの抗腫瘍細胞増殖能 (2009)
  • Author(s): 石川吉伸
  • Organizer: 静岡県立大学 2008USフォーラム
  • Place of Presentation: 静岡県立大学
  • Year and Date: 2009-08-04
• [Presentation] 膜タンパク質ストマチンの三次元構造 (2009)
  • Author(s): 横山英志
  • Organizer: 第55回日本薬学会東海支部総会・大会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-07-11
• [Presentation] 膜タンパク質ストマチンの三次元構造 (2009)
  • Author(s): 横山英志
  • Organizer: 第55回日本薬学会東海支部総会・大会(名古屋)
  • Place of Presentation: 名古屋市立大学
  • Year and Date: 2009-07-11
• [Presentation] インフルエンザウィルス由来金属酵素RNAポリメラーゼに対するジケト酸誘導体の分子ドッキングによる結合様式予測 (2009)
  • Author(s): 石川吉伸、藤井敏
  • Organizer: 第19回金属の関与する生体関連反応シンポジウム
  • Place of Presentation: 大阪
  • Year and Date: 2009-06-12
• [Presentation] インフルエンザウィルス由来金属酵素RNAポリメラーゼに対するジケト酸誘導体の分子ドッキングによる結合様式予測 (2009)
  • Author(s): 石川吉伸, 藤井敏
  • Organizer: 第19回金属の関与する生体関連反応シンポジウム
  • Place of Presentation: 大阪大学
  • Year and Date: 2009-06-12
• [Remarks]
  • URL: http://w3pharm.u-shizuoka-ken.ac.jp/.bukka/ishikawa/index.html
• [Remarks]
  • URL: http://db.u-shizuoka-ken.ac.jp/show/prof331.html
• [Remarks]
  • URL: http://db.u-shizuoka-ken.ac.jp/show/prof331.html
• [Remarks]
  • URL: http://db.u-shizuoka-ken.ac.jp/show/prof331.html