Development of a novel therapeutic agent against Influenza virus infections using multivalent peptide library techniques

• Project/Area Number: 18390044
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Environmental pharmacy
• Research Institution: Doshisha University (2007-2008); Research Institute, International Medical Center of Japan (2006)
• Principal Investigator: NISHIKAWA Kiyotaka Doshisha University, 生命医科学部, 教授 (40218128)
• Project Period (FY): 2006 – 2009
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,050,000 (Direct Cost: ¥15,200,000、Indirect Cost: ¥2,850,000); Fiscal Year 2008: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2007: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2006: ¥5,700,000 (Direct Cost: ¥5,700,000)
• Keywords: 薬学 / 感染症 / 糖鎖 / 衛生 / 蛋白質

Research Abstract

A型インフルエンザウイルスの表面タンパク質であるHAは3量体を形成することで非常に強く標的細胞に結合する(クラスター効果). 本研究では, このクラスター効果に基づく高親和性結合を阻害する阻害剤を開発するための新しい方法, 多価型ペプチドライブラリー法を用いて, HA3量体に特異的かつ高親和性に結合するペプチドモチーフを同定した。本モチーフを有する化合物は,ウイルス粒子の標的細胞への侵入を強力に阻害するペプチド性阻害剤として期待される.

Research Products

• [Journal Article] Yip1A regulates the COPI-independent retrograde transport from the Golgi apparatus to the endoplasmic reticulum (2009)
  • Author(s): Kano F., Yamauchi S., Yoshida Y., Watanabe-Takahashi M., Nishikawa K., Nakamura N., and Murata M
  • Journal Title: J. Cell Sci. (in press)
  • Peer Reviewed
• [Journal Article] Yip1A regulates the COPI-independent retrograde transport from the Golgi apparatus to the endoplasmic reticulum. (2009)
  • Author(s): Kano F, Yamauchi S., Yoshida Y., Watanabe-Takahashi M., Nishikawa K., Nakamura N., Murata M.
  • Journal Title: J. Cell Sci. (in press)
  • Peer Reviewed
• [Journal Article] 腸管出血性大腸菌(EHEC)による感染への新たな対策の研究 (2008)
  • Author(s): 西川喜代孝
  • Journal Title: 化学療法の領域(医薬ジャーナル社) 24(5) Pages: 93-101
• [Journal Article] 志賀毒素の細胞内輸送異常を誘導するペプチド (2008)
  • Author(s): 西川喜代孝
  • Journal Title: 蛋白質核酸酵素(共立出版) 53(1) Pages: 44-51
  • NAID: 40015771164
• [Journal Article] Type I platelet-activating factor acetylhydrolase catalytic subunits over-expression induces pleiomorphic nuclei and centrosome amplification (2007)
  • Author(s): Yamaguchi N., Koizumi H., Aoki J., Natori Y., Nishikawa K., Natori Y., Takanezawa Y., and Arai H.
  • Journal Title: Genes Cells 12 Pages: 1153-1161
  • Peer Reviewed
• [Journal Article] O157感染症に対する次世代治療薬の開発 (2007)
  • Author(s): 西川喜代孝
  • Journal Title: 小児感染免疫(日本小児感染症学会) 19(1) Pages: 75-83
  • NAID: 10018885718
• [Journal Article] Type I platelet-activating factor acetylhydrolase catalytic subunits over-expression induces pleiomorphic nuclei and centroso me amplification (2007)
  • Author(s): Yamaguchi N., Koizumi H., Aoki J., Natori Y., Nishikawa K., Natori Y., Takanezawa Y., and Arai H.
  • Journal Title: Genes Cells 12 Pages: 1153-1161
  • Peer Reviewed
• [Journal Article] A multivalent peptide-library approach identifies a novel Shiga toxin-inhibitor that induces aberrant cellular transport of the toxin (2006)
  • Author(s): Nishikawa K.*, Watanabe M., Kita E., Igai K., Omata K., Yaffe M. B., and Natori Y
  • Journal Title: FASEB J. 20 Pages: 2597-2599
  • Peer Reviewed
• [Journal Article] Regulation of hepatic cholesterol synthesis by a novel protein (SPF) that accelerates cholesterol biosynthesis (2006)
  • Author(s): Shibata N., Jishage K., Arita M., Watanabe M., Kawase Y., Nishikawa K., Natori Y., Inoue H., Shimano H., Yamada N., Tsujimoto M., and Arai H.
  • Journal Title: FASEB J. 20 Pages: 2642-2644
  • Peer Reviewed
• [Journal Article] Histidine-tagged Shiga toxin B subunit binding assay : Simple and specific determination of Gb3 content in mammalian cells (2006)
  • Author(s): Shin I., Nishikawa K., Maruya H., and Ishii S.
  • Journal Title: Chem. Pharm. Bull. 54 Pages: 522-527
  • NAID: 110004820427
  • Peer Reviewed
• [Journal Article] Syntheses and Vero toxin-binding activities of carbosilane dendrimers periphery-functionalized with galabiose (2006)
  • Author(s): Yamada A., Hatano K., Matsuoka K., Koyama T., Esumi Y., Koshino H., Hino K., Nishikawa K., Natori Y., and Terunuma D.
  • Journal Title: Tetrahedron 62 Pages: 5074-5083
  • Peer Reviewed
• [Journal Article] Development of dialyzer with immobilized glycoconjugate polymers for removal of Shiga-toxin (2006)
  • Author(s): Miyagawa A., Watanabe M., Igai K., Kasuya M. C. Z., Natori Y., Nishikawa K., and Hatanaka K.
  • Journal Title: Biomaterials 27 Pages: 3304-3311
  • Peer Reviewed
• [Journal Article] Structural analysis of the interaction between Shiga toxin B-subunits and linear polymers bearing clustered globotriose residues (2006)
  • Author(s): Watanabe M., Igai K., Matsuoka K., Miyagawa A., Watanabe T., Yanoshita R., Samejima Y., Terunuma D., Natori Y, and Nishikawa K.
  • Journal Title: Infect. Immun. 74 Pages: 1984-1988
  • Peer Reviewed
• [Journal Article] 腸管出血性大腸菌感染症 (2006)
  • Author(s): 西川喜代孝
  • Journal Title: Pharma Medica(メディカルレビュー社) 24(8) Pages: 33-37
• [Journal Article] ベロ毒素を標的としたO157感染症治療薬 (2006)
  • Author(s): 西川喜代孝
  • Journal Title: ファルマシア(日本薬学会) 42(4) Pages: 319-323
• [Journal Article] A multivalent peptide-library approach identifies a novel Shiga toxin-inhibitor that induces aberrant cellular transport of the toxin (2006)
  • Author(s): Nishikawa K.
  • Journal Title: FASEB J 20 Pages: 2597-2599
• [Journal Article] Regulation of hepatic cholesterol synthesis by a novel protein(SPF) that accelerates cholesterol biosynthesis (2006)
  • Author(s): Shibata N.
  • Journal Title: FASEB J. 20 Pages: 2642-2644
• [Journal Article] Histidine-tagged Shiga toxin b sbunit bindinf assay : simple and specfic determination of Gc3 content in mammalian cells (2006)
  • Author(s): Shin I.
  • Journal Title: Chem,Pharm.Bull 54 Pages: 522-527
• [Journal Article] syntheses anddVervo toxin-binding activities of carbosilance dendrimers periphery-functionalized with galabiose. (2006)
  • Author(s): Yamada A.
  • Journal Title: Tetrahedron 62 Pages: 5074-5083
• [Journal Article] Development o f dialyzer with im mobilized glycoconjugate polymers for removal of Shiga-toxin. (2006)
  • Author(s): Miyagawa A.
  • Journal Title: Biomaterials 27 Pages: 3304-3311
• [Journal Article] structural analysis of the interaction between Shiga toxin B-subunits and linear polymers bearing clustered globotriose residues. (2006)
  • Author(s): Watanabe M.
  • Journal Title: Infect.Immun. 74 Pages: 1984-1988
• [Presentation] テーマ「革新的な抗体・核酸・ペプチド医薬への展望」演題名-クラスター効果に基づく強い相互作用を阻害する技術-多価型ペプチドライブラリー法 (2009)
  • Author(s): 高橋美帆、西川喜代孝
  • Organizer: 第82回日本細菌学会総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2009-03-13
• [Presentation] クラスター効果に基づく強い相互作用を阻害する技術-多価型ペプチドライブラリー法 (2009)
  • Author(s): 高橋美帆, 西川喜代孝
  • Organizer: 第82回日本細菌学会総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2009-03-13
• [Presentation] 特別講演「O157感染症の新規治療薬の創製」 (2008)
  • Author(s): 西川喜代孝
  • Organizer: 第82回日本感染症学会総会
  • Place of Presentation: 島根県民会館
  • Year and Date: 2008-04-17
• [Presentation] ランチョンセミナー「細菌毒素に結合する中和ペプチドのデザインとその効果」 (2008)
  • Author(s): 西川喜代孝
  • Organizer: 第81回日本細菌学会総会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2008-03-25
• [Presentation] 細菌毒素に結合する中和ペプチドのデザインとその効果 (2008)
  • Author(s): 西川 喜代孝
  • Organizer: 第81回日本細菌学会総会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2008-03-25
• [Presentation] テーマ「安全で健康な生活を目指してー食の安全・機能性と創薬研究における産学連携・関西からの発信」演題名「腸管出血性大腸菌感染症に対する次世代治療薬の開発」 (2007)
  • Author(s): 西川喜代孝
  • Organizer: 大阪府立大学産学官連携機構生物資源開発センターセミナー
  • Place of Presentation: 大阪府立大学
  • Year and Date: 2007-10-12
• [Presentation] 腸管出血性大腸菌感染症に対する次世代治療薬の開発 (2007)
  • Author(s): 西川 喜代孝
  • Organizer: 大阪府立大学産学官連携機構生物資源開発センターセミナー
  • Place of Presentation: 大阪府立大学
  • Year and Date: 2007-10-12
• [Presentation] テーマ「腸管出血性大腸菌感染症の治療」演題名-「重症合併症予防の最先端-新しい志賀毒素阻害薬を中心にー」 (2006)
  • Author(s): 西川喜代孝
  • Organizer: 第10回腸管出血性大腸菌感染症シンポジウム
  • Place of Presentation: 東京慈恵医科大
  • Year and Date: 2006-09-01
• [Presentation] 6^<th> International Symposium on "Shiga toxin (Verocytotoxin)-producing (2006)
  • Author(s): Neutralizing Shiga toxin., Nishikawa, K
  • Organizer: Escherichia coli Infections
  • Place of Presentation: Melbourne, Australia
• [Presentation] A novel Shiga toxin neutralizer for treatment of STEC infections (2006)
  • Author(s): Nishikawa, K.
  • Organizer: International Symposium on Cholera and Other Diarrhoeal Diseases
  • Place of Presentation: Kolkata, India
• [Presentation] Structural analysis of the interaction between Shiga toxin B-subunits and linear polymers bearing clustered globotriose residues (2006)
  • Author(s): Watanabe M., Igai K., Matsuoka K., Miyagawa A., Watanabe T., Yanoshita R., Samejima Y., Terunuma D., Natori Y, and Nishikawa K
  • Organizer: 6^<th> International Symposium on "Shiga toxin (Verocytotoxin)-producing Escherichia coli Infections"
  • Place of Presentation: Melbourne, Australia, Poster presentation
• [Presentation] A multivalent peptide-library approach identifies an inhibitor for a sugar-recognizing molecule, Shiga toxin (2006)
  • Author(s): Nishikawa K., Kita E., Omata K., Igai K., Watanabe M., Yaffe M. B., Natori Y.
  • Organizer: 20^<th> IUBMB International Congress of Biochemistry and Molecular Biology and 11^<th> FAOBMB Congress
  • Place of Presentation: Kyoto, Japan, Poster presentation
• [Presentation] 出展タイトルー腸管出血性大腸菌感染症に対する次世代治療薬を開発する (2006)
  • Author(s): 西川喜代孝
  • Organizer: さきがけライブ2006、(独)科学技術振興機構主催
  • Place of Presentation: 東京国際フォーラム
• [Remarks] JST、研究成果展開総合データベースJ-STORE(http://jstore.jst.go.jp/) 掲載分特許出願番号2006-528873、毒素中和性ペプチドのスクリーニング方法とSTX2阻害性ペプチド並びにベロ毒素中和剤
  • URL: http://jstore.jst.go.jp/cgi-bin/patent/advanced/detail.cgi?pat_id=19242
• [Remarks]
  • URL: http://jstore.ist.go.jp/cgi-bin/patent/advanced/detail.cgi?pat_id=19242
• [Remarks]
  • URL: http://jstore.ist.go.jp/cgibin/patent/advanced/pat/detail_pat.cgi?patid=19242&detail_id=22729
• [Patent(Industrial Property Rights)] Japan Science and Technology Agency (2009)
  • Inventor(s): Nishikawa, Kiyotaka
  • Industrial Property Rights Holder: Method of screening toxin-neutralizing peptide, STX2 inhibitory peptide and vero toxin-neutralizing agent
  • Filing Date: 2009-01-29
• [Patent(Industrial Property Rights)] Method of screening toxin-neutralizing peptide, STX2 inhibitory peptide and vero toxin-neutralizing agent (2009)
  • Inventor(s): Nishikawa, Kiyotaka
  • Industrial Property Rights Holder: Japan Science, Technology Agency
  • Acquisition Date: 2009-01-29
  • Overseas