Development of a novel Shiga toxin inhibitor that targeting of intracellular transport of the toxin

• Project/Area Number: 15K08480
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Bacteriology (including mycology)
• Research Institution: Doshisha University
• Principal Investigator: Takahashi Miho 同志社大学, 生命医科学部, 助教 (00446569)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 志賀毒素 / 細胞内小胞輸送 / ペプチド / 阻害剤 / ペプチドライブラリー / 腸管出血性大腸菌 / 感染症 / キナーゼ基質アレイ / 小胞輸送 / Stx阻害ペプチド

Outline of Final Research Achievements

We synthesized substrate peptides of various kinases on a slide glass and using this, we analyzed the activities of kinases stimulated by Stx1a in the presence or absence of Stx inhibitors (MMA-tet, FRA-tet).We established a new multivalent peptide library screening by using tetravalent peptides synthesized on a cellulose membrane.

Research Products

• [Journal Article] Pleckstrin homology domain of p210 BCR-ABL interacts with cardiolipin to regulate its mitochondrial translocation and subsequent mitophagy (2018)
  • Author(s): Shimasaki K, Watanabe-Takahashi M, Umeda M, Funamoto S, Saito Y, Noguchi N, Kumagai K, Hanada K, Tsukahara F, Maru Y, Shibata N, Naito M, Nishikawa K.
  • Journal Title: Genes to Cells Volume: 23 Issue: 1 Pages: 22-34
  • DOI: 10.1111/gtc.12544
  • Peer Reviewed / Open Access
• [Journal Article] Affinity-based screening of tetravalent peptides identifies subtype-selective neutralizers of Shiga toxin 2d, a highly virulent subtype, by targeting a unique amino acids involved in its receptor recognition. (2016)
  • Author(s): Mitsui T., Watanabe-Takahashi M., Shimizu E., Zhang B., Funamoto S., Yamasaki S., Nishikawa K.
  • Journal Title: Infection and Immunity Volume: 84 Pages: 2653-2661
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Identification of a wide range of motifs inhibitory to Shiga toxin by affinity-driven screening of customized divalent peptides synthesized on a membrane (2015)
  • Author(s): 1) Kato M., Watanabe-Takahashi M., Shimizu E., and Nishikawa K.
  • Journal Title: Appl. Environ. Microbiol. Volume: 81 Issue: 3 Pages: 1092-1100
  • DOI: 10.1128/aem.03517-14
  • Peer Reviewed / Acknowledgement Compliant
• [Patent(Industrial Property Rights)] ヘマグルチニン結合ペプチド、および、これを含むインフルエンザウイルス感染症の予防・治療薬 (2017)
  • Inventor(s): 西川喜代孝、髙橋美帆、近江純平
  • Industrial Property Rights Holder: 西川喜代孝、髙橋美帆、近江純平
  • Industrial Property Rights Type: 特許
  • Filing Date: 2017
• [Patent(Industrial Property Rights)] ヘマグルチニン結合ペプチド、および、これを含むインフルエンザウイルス感染症の予防・治療薬 (2016)
  • Inventor(s): 西川喜代孝、高橋美帆、近江純平、他４名
  • Industrial Property Rights Holder: 学校法人同志社
  • Industrial Property Rights Type: 特許
  • Filing Date: 2016-08-25