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Creation of novel Catalytide with In Silico

Research Project

Project/Area Number 19K22499
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 47:Pharmaceutical sciences and related fields
Research InstitutionKochi University

Principal Investigator

Akizawa Toshifumi  高知大学, 医学部, 特任教授 (30202526)

Project Period (FY) 2019-06-28 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
KeywordsCatalytide / アルツハイマー病 / 神経変性疾患 / 酵素ペプチド / ALS / パーキンソン病 / In silico / コンピュータモデリング / 凝集性タンパク質 / SOD1 / peptide / Alzheimer's disease / ドッキングシミュレーション / Peptide / Amyloid-beta / ペプチド性加水分解酵素 / In Silico / ベーターアミロイド / アルツハイマー病治療薬
Outline of Research at the Start

申請者らの発見した加水分解酵素活性を有する5-9 アミノ酸よりなる短鎖合成ペプチド (Catalytide) はこれまでの治療戦略とは異なった新規ストラテジーによるアルツハイマー病の根本的な治療となり得る。本研究では Catalytide に関する未発表データーも併用し、立体構造-活性相関を詳細に解析することで、PC による臨床適用可能な新規Catalytideを創造する方法論を確立する。本研究の成果は、アルツハイマー病のみならず、パーキンソン病やALSにも適用できる可能性が高い。さらに、学術的観点からは加水分解解酵素反応機構の解明に有益な情報(データ)を得ることができる。

Outline of Final Research Achievements

To find the novel Catalytide in Silico, we analyzed the stereo-structure of Catalytides by Personal Computer (PC)with MM2 and MMFF94 parameters. As the results, we determined the active center amino acid and stereo-structure required for activity. We next tried to identify the novel Catalytide. We applied our finding to 5-mer Catalytide, GSGHR, that the most effective protease against Aβ11-29 and several kinds of that derivatives including D-amino acid in the molecule. As the results, we identified the novel Catalytide. This study indicated that Catalytide can be created with ease in Silico by PC with MM2 and MMFF94 parameters without supercomputer. We are now trying to the novel Catalytide being applicable for SARS-CoV-2 spike.

Academic Significance and Societal Importance of the Research Achievements

Catalytide は新規性が極めて高く、特に5 残基ペプチドは誘導体も含め合成は極めて簡単で、PC による構造解析も酵素タンパク質と異なり短時間でできる。申請者らの保有する 70 種を超える 5 残基ペプチドの立体構造を PC で解析し、酵素活性に必要なアミノ酸の空間的位置関係を解析することで、新規 Catalytide の創造が可能となる。本研究の成果は、これまでの治療薬とは全くストラテジーの異なった日本発の根本的なアルツハイマー病治療薬の開発のみでなく、凝集性タンパク質が発症原因となるパーキンソン病、ALS、プリオン、IgA 腎症などの治療薬開発に繋がることも期待できる。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (23 results)

All 2021 2020 2019

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 6 results) Presentation (15 results) (of which Int'l Joint Research: 4 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Direct Delivery of ANA-TA9, a Peptide Capable of Aβ Hydrolysis, to the Brain by Intranasal Administration2021

    • Author(s)
      Hatakawa Yusuke、Tanaka Akiko、Furubayashi Tomoyuki、Nakamura Rina、Konishi Motomi、Akizawa Toshifumi、Sakane Toshiyasu
    • Journal Title

      Pharmaceutics

      Volume: 13 Issue: 10 Pages: 1673-1673

    • DOI

      10.3390/pharmaceutics13101673

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Amyloid beta cleavage by ANA‐TA9, a synthetic peptide from the ANA/BTG3 Box A region2021

    • Author(s)
      Hatakawa Yusuke、Nakamura Rina、Konishi Motomi、Sakane Toshiyasu、Tanaka Akiko、Matsuda Akira、Saito Motoaki、Akizawa Toshifumi
    • Journal Title

      Alzheimer's & Dementia: Translational Research & Clinical Interventions

      Volume: 7 Issue: 1

    • DOI

      10.1002/trc2.12146

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] JAL-TA9 Inhibits Aggregation of Hprp180-192 through the Cleavage Reaction2020

    • Author(s)
      Nakamura Rina、Konishi Motomi、Sakaguchi Yuko、Hatakawa Yusuke、Tanaka Akiko、Sakane Toshiyasu、Saito Motoaki、Akizawa Toshifumi
    • Journal Title

      Journal of Pharmacy and Pharmacology Research

      Volume: 04 Issue: 02 Pages: 23-33

    • DOI

      10.26502/fjppr.029

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evaluation of the proteolytic activity of 5-mer peptides in BoxA region of Top/BTG family proteins against Amyloid-β fragment peptides2020

    • Author(s)
      Rina Nakamura, Motomi Konishi, Yusuke Hatakawa, Saito Motoaki, Toshifumi Akizawa
    • Journal Title

      Peptide Science 2019, The Japanese Peptide Society

      Volume: -

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Catalytides derived from the Box A region in the ANA/BTG3 protein cleave amyloid-β fragment peptide2019

    • Author(s)
      Hatakawa Yusuke、Nakamura Rina、Konishi Motomi、Sakane Toshiyasu、Saito Motoaki、Akizawa Toshifumi
    • Journal Title

      Heliyon

      Volume: 5 Issue: 9 Pages: e02454-e02454

    • DOI

      10.1016/j.heliyon.2019.e02454

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Novel Catalytic Peptide, A Synthetic Nona-Peptide (JAL-TA9) Derived from Tob1 Protein, Digests the Amyloid Peptide2019

    • Author(s)
      Nakamura Rina, Konishi Motomi, Hatakawa Yusuke, Saito Motoaki, Akizawa Toshifumi
    • Journal Title

      Journal of Royal Science

      Volume: 1 Pages: 30-35

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparison of the catalytic activities of 5-mer synthetic peptides derived from Box A region of Tob/BTG family proteins against the amyloid-beta fragment peptides2019

    • Author(s)
      Nakamura Rina、Konishi Motomi、Higashi Youichirou、Saito Motoaki、Akizawa Toshifumi
    • Journal Title

      Integrative Molecular Medicine

      Volume: 6 Issue: 4 Pages: 1-4

    • DOI

      10.15761/imm.1000374

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Effects of 9-Mer Catalytide, JAL-TA9 to APP Knock-in Mice through the Single Direction Dose into Hippocampus2021

    • Author(s)
      R. Nakamura, Y. Higashi, T. Aratake, M. Konishi, M. Saito, T. Akizawa
    • Organizer
      International Conference on Alzheimer's and Parkinson's Diseases and related neurological disorders
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 低分子ペプチドを用いたタンパク質変性による神経変性疾患の治療の開発2021

    • Author(s)
      中村里菜
    • Organizer
      Bio Japan 2021
    • Related Report
      2021 Annual Research Report
  • [Presentation] パーキンソン病 (PD) 治療薬開発に向けたシーズペプチドの同定2021

    • Author(s)
      中村里菜、小西元美、齊藤源顕、秋澤俊史
    • Organizer
      第 21 回 KMS リサーチミーティング
    • Related Report
      2021 Annual Research Report
  • [Presentation] SOD1 を標的とした ALS の根本的治療薬の開発-SOD1 凝集の核となるペプチドの同定と凝集抑制ペプチドのスクリーニング-2021

    • Author(s)
      坂田大輔、谷口大樹、中村里菜、齊藤源顕、秋澤俊史
    • Organizer
      第 21 回 KMS リサーチミーティング
    • Related Report
      2021 Annual Research Report
  • [Presentation] Tau を標的としたアルツハイマー病治療薬の開発-Tau 凝集の核となるペプチドの同定と凝集抑制ペプチドのスクリーニング-2021

    • Author(s)
      谷口大樹、坂田大輔、中村里菜、齊藤源顕、秋澤俊史
    • Organizer
      第 21 回 KMS リサーチミーティング
    • Related Report
      2021 Annual Research Report
  • [Presentation] Alzheimer's model mouse を用いた 9 残基酵素ペプチド JAL-TA9 脳内投与の効果2021

    • Author(s)
      中村里菜、小西 元美、新武 享明、東 洋一郎、齊藤 源顕、秋澤 俊史
    • Organizer
      第 20 回 KMS Research Meeting
    • Related Report
      2020 Research-status Report
  • [Presentation] Effects of 9-Mer Catalytide, JAL-TA9 to APP Knock-in Mice through the Single Direction Dose into Hippocampus2021

    • Author(s)
      Rina Nakmaura, Youichirou Higashi, Takaaki Aratake, Motomi Konishi, Motoaki Saito, Toshifumi Akizawa
    • Organizer
      International Conference on Alzheimer's and Parkinson's Diseases and related neurological disorders
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Alzheimer's model mouse を用いた 9 残基酵素ペプチド JAL-TA9 脳内投与の効果2020

    • Author(s)
      中村 里菜、小西 元美、新武 享明、東 洋一郎、齊藤 源顕、秋澤 俊史
    • Organizer
      第 39 回日本認知症学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] Catalytide improves the cognitive deficits by injecting into the CA1 of hippocampus in Alzheimer's disease model mice2020

    • Author(s)
      Rina Nakamura, Youichirou Higashi, Takaaki Aratake, Motomi Konishi, Yusuke Hatakawa, Motoaki Saito, Toshifumi Akizawa
    • Organizer
      Cold Spring Haver
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Tob/BTG ファミリータンパク質 BoxA 領域由来フラグメントペプチドの加水分解酵素2019

    • Author(s)
      中村里菜、小西元美、齊藤源顕、秋澤俊史
    • Organizer
      病態プロテアーゼ学会
    • Related Report
      2019 Research-status Report
  • [Presentation] フラグメントペプチドを用いた Tob/BTG ファミリータンパク質 BoxA ドメインの機能解析2019

    • Author(s)
      中村里菜、小西元美、齊藤源顕、秋澤俊史
    • Organizer
      第 32 回 バイオメディカル分析科学シンポジウム (BMAS)
    • Related Report
      2019 Research-status Report
  • [Presentation] 5 残基 Catalytide (RHGSG) とAβ1-20 とのドッキングシュミレーション2019

    • Author(s)
      山本隆幸、小西元美、中村里菜、秋澤俊史
    • Organizer
      第 32 回 バイオメディカル分析科学シンポジウム (BMAS)
    • Related Report
      2019 Research-status Report
  • [Presentation] 5 残基 Catalytide (RYGSG) とAβ11-29 とのドッキングシュミレーション2019

    • Author(s)
      大西航平、小西元美、中村里菜、秋澤俊史
    • Organizer
      第 32 回 バイオメディカル分析科学シンポジウム (BMAS)
    • Related Report
      2019 Research-status Report
  • [Presentation] Evaluation of the proteolytic activity of 5-mer peptides in BoxA region of Top/BTG family proteins against Amyloid-β fragment peptides2019

    • Author(s)
      Rina Nakamura, Motomi Konishi, Yusuke Hatakawa, Saito Motoaki, Toshifumi Akizawa
    • Organizer
      第 56 回ペプチド討論会
    • Related Report
      2019 Research-status Report
  • [Presentation] Creating the novel proteolytic peptide (Catalytide) extracting from protein enzyme2019

    • Author(s)
      Rina Nakamura, Yusuke Hatakawa, Motomi Konishi, Saito Motoaki, Toshifumi Akizawa
    • Organizer
      11th General Meeting of the International Proteolysis Society
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Patent(Industrial Property Rights)] アミロイドβの凝集抑制剤、アミロイドβ凝集疾患用医薬組成物、及びその用途2020

    • Inventor(s)
      秋澤俊史、齊藤源顕、東洋一郎、中村里菜
    • Industrial Property Rights Holder
      秋澤俊史、齊藤源顕、東洋一郎、中村里菜
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-167404
    • Filing Date
      2020
    • Related Report
      2020 Research-status Report

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Published: 2019-07-04   Modified: 2023-01-30  

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