• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Directed evolution of cyclized N-alkyl peptides targeted to cellular biomolecules

Research Project

Project/Area Number 25870146
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Chemical biology
Bio-related chemistry
Research InstitutionNational Institute of Advanced Industrial Science and Technology (2014-2015)
The University of Tokyo (2013)

Principal Investigator

Kawakami Takashi  国立研究開発法人産業技術総合研究所, 創薬分子プロファイリング研究センター, 研究員 (60638881)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsPUREシステム / mRNAディスプレイ / Nメチルペプチド / Elongation factor P / 分子進化 / ペプトイド / Nアルキルペプチド / プロテオミクス / 抗体 / Nアルキルアミノ酸 / ペプチド / リボソーム / ケミカルバイオロジー / タンパク質 / tRNA / リガンド
Outline of Final Research Achievements

By the addition of elongation factor P (EF-P) to an E. coli reconstituted cell-free translation system, PURE system (Protein-synthesis Using Recombinant Elements systen), we successfully evaluated translation efficiency of cyclic N-alkyl amino acids in a library of mRNA-displayed highly N-alkylated polycyclic peptidomimetics.
By using bio-orthognal chemical reaction or enzymatic reaction, we developed a novel method to incorporate electorically-charged N-alkyl amino acids to ribosomally synthesized peptides.
By combining the PURE system with an mRNA display method, we successfully in vitro-evolved cyclized N-alkyl peptides targeted to VEGFR2 expressed in living human cells.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (36 results)

All 2016 2015 2014 2013 Other

All Journal Article (10 results) (of which Peer Reviewed: 10 results,  Open Access: 1 results,  Acknowledgement Compliant: 3 results) Presentation (19 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results) Book (1 results) Remarks (4 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Directed Evolution of a Cyclized Peptoid-Peptide Chimera against a Cell-Free Expressed Protein and Proteomic Profiling of the Interacting Proteins to Create a Protein-Protein Interaction Inhibitor2016

    • Author(s)
      Takashi Kawakami, Koji Ogawa, Tomohisa Hatta, Naoki Goshima, and Tohru Natsume
    • Journal Title

      ACS Chemical Biology

      Volume: 11 Issue: 6 Pages: 1569-77

    • DOI

      10.1021/acschembio.5b01014

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Post-translational modification mapping of collagen that binds to HSP47 by directed ligand evolution and DNLC mass spectrometry2015

    • Author(s)
      Takashi Kawakami, Shinya Ito, Naoki Goshima, Kazuhiro Nagata, and Tohru Natsume
    • Journal Title

      Peptide Science

      Volume: 52 Pages: 321-322

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In vitro display evolution of cyclized peptidomimetics targeted to a chemically synthesized amyloid beta protein dimer2015

    • Author(s)
      Takashi Kawakami, Kazuma Murakami, Daiki Sakamoto, Mizuho Hanaki, Tohru Natsume, and Kazuhiro Irie
    • Journal Title

      Peptide Science

      Volume: 52 Pages: 323-324

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Proteomic Mapping of Biological Complexes Using Directed Ligand Evolution and Ultra-High Sensitive Mass Spectrometry2015

    • Author(s)
      Takashi Kawakami, Shungo Adachi, Koji Ogawa, Tomohisa Hatta, Tai Kubo, Naoki Goshima, Tohru Natsume
    • Journal Title

      Peptide Science

      Volume: 51 Pages: 339-340

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Directed Evolution of tRNA-Aminophosphonating Ribozymes for Ribosomal Phosphono-Peptide Synthesis2015

    • Author(s)
      Takashi Kawakami
    • Journal Title

      Peptide Science

      Volume: 51 Pages: 337-338

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Ribosomal incorporation of diverse cyclic N-alkyl amino acids2014

    • Author(s)
      Takashi Kawakami, Takahiro Ishizawa, Hiroshi Murakami
    • Journal Title

      Peptide Science

      Volume: 50 Pages: 427-428

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Ribosomal synthesis of charged N-alkyl amino acid-containing peptides2014

    • Author(s)
      Takashi Kawakami, Toru Sasaki, Patrick C. Reid, Hiroshi Murakami
    • Journal Title

      Peptide Science

      Volume: 50 Pages: 423-424

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Incorporation of electrically charged N-alkyl amino acids into ribosomally synthesized peptides via post-translational conversion2014

    • Author(s)
      Takashi Kawakami, Toru Sasaki, Reid C. Patrick, Hiroshi Murakami
    • Journal Title

      Chemical Science

      Volume: 5 Issue: 3 Pages: 887-893

    • DOI

      10.1039/c3sc52744a

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Patch cloning method for multiple site-directed and saturation mutagenesis2013

    • Author(s)
      Naohiro Taniguchi, Sayumi Nakayama, Takashi Kawakami, Hiroshi Murakami
    • Journal Title

      BMC Biotechnology

      Volume: 13 Issue: 1

    • DOI

      10.1186/1472-6750-13-91

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Extensive reprogramming of the genetic code for genetically encoded synthesis of highly N-alkylated polycyclic peptidomimetics2013

    • Author(s)
      Takashi Kawakami, Takahiro Ishizawa, Hiroshi Murakami
    • Journal Title

      Journal of the American Chemical Society

      Volume: 135 Issue: 33 Pages: 12297-12304

    • DOI

      10.1021/ja405044k

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 試験管内分子進化法を用いたPPI阻害環状Nアルキルペプチド化合物の創製2016

    • Author(s)
      川上隆史
    • Organizer
      新学術領域研究「天然物ケミカルバイオロジー」地区ミニシンポジウム~天然物ケミカルバイオロジーの更なる発展を目指して~
    • Place of Presentation
      京都大学(京都府京都市)
    • Year and Date
      2016-02-23
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Directed evolution of antibody-like peptides for proteomics2015

    • Author(s)
      Takashi Kawakami, Naoki Goshima, and Tohru Natsume
    • Organizer
      The 2015 International Chemical Congress of Pacific Basin Societies
    • Place of Presentation
      Honolulu (USA)
    • Year and Date
      2015-12-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 無細胞分子進化法と超高感度質量分析を用いた翻訳後修飾の網羅的解析2015

    • Author(s)
      川上隆史、伊藤進也、五島直樹、永田和宏、夏目徹
    • Organizer
      日本ペプチド学会第52回ペプチド討論会
    • Place of Presentation
      平塚中央公民館(神奈川県平塚市)
    • Year and Date
      2015-11-16
    • Related Report
      2015 Annual Research Report
  • [Presentation] アミロイドβ二量体を標的とする非天然型環状ペプチドの試験管内分子進化2015

    • Author(s)
      川上隆史、村上一馬、阪本大樹、花木瑞穂、夏目徹、入江一浩
    • Organizer
      日本ペプチド学会第52回ペプチド討論会
    • Place of Presentation
      平塚中央公民館(神奈川県平塚市)
    • Year and Date
      2015-11-16
    • Related Report
      2015 Annual Research Report
  • [Presentation] 進化分子工学と有機合成化学を基盤とするペプチドツール創製システムの構築2015

    • Author(s)
      川上隆史
    • Organizer
      BioJapan2015 World Business Forum
    • Place of Presentation
      パシフィコ横山(神奈川県横浜市)
    • Year and Date
      2015-10-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] タンパク質ラベリング用ペプチドタグの進化分子工学的創製システムの構築2015

    • Author(s)
      川上隆史、五島直樹、夏目徹
    • Organizer
      日本ケミカルバイオロジー学会第10回年会
    • Place of Presentation
      東北大学(宮城県仙台市)
    • Year and Date
      2015-06-10
    • Related Report
      2015 Annual Research Report
  • [Presentation] プロテオミクスアプローチによるタンパク質間相互作用阻害剤の同定2015

    • Author(s)
      川上隆史、五島直樹、夏目徹
    • Organizer
      「天然物ケミカルバイオロジー~分子標的と活性制御~」第8回公開シンポジウム
    • Place of Presentation
      東北大学(宮城県仙台市)
    • Year and Date
      2015-06-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] Directed Evolution of Natural Product-Like Peptides2014

    • Author(s)
      Takashi Kawakami, Naoki Goshima, Tohru Natsume
    • Organizer
      The 3rd International Symposium on Chemical Biology of Natural Products: Target ID and Regulation of Bioactivity
    • Place of Presentation
      Osaka
    • Year and Date
      2014-10-28 – 2014-10-29
    • Related Report
      2014 Research-status Report
  • [Presentation] 試験管内分子進化と超高感度質量分析を用いた蛋白質複合体の解析2014

    • Author(s)
      川上隆史、足達俊吾、小川浩二、八田知久、久保泰、五島直樹、夏目徹
    • Organizer
      第51回ペプチド討論会
    • Place of Presentation
      徳島
    • Year and Date
      2014-10-22 – 2014-10-24
    • Related Report
      2014 Research-status Report
  • [Presentation] ホスホノペプチドの翻訳合成に向けたtRNAアミノホスホニル化リボザイムの分子進化2014

    • Author(s)
      川上隆史
    • Organizer
      第51回ペプチド討論会
    • Place of Presentation
      徳島
    • Year and Date
      2014-10-22 – 2014-10-24
    • Related Report
      2014 Research-status Report
  • [Presentation] 天然物様ペプチドライブラリーからのリガンド探索法の開発2014

    • Author(s)
      川上隆史、五島直樹、夏目徹
    • Organizer
      「天然物ケミカルバイオロジー~分子標的と活性制御~」;第6回公開シンポジウム
    • Place of Presentation
      名古屋
    • Year and Date
      2014-05-28 – 2014-05-29
    • Related Report
      2014 Research-status Report
  • [Presentation] Ribosomal incorporation of diverse cyclic N-alkyl amino acids2013

    • Author(s)
      Takashi Kawakami, Takahiro Ishizawa, Hiroshi Murakami
    • Organizer
      The 4th Asia-Pacific International Peptide Symposium
    • Place of Presentation
      ホテル阪急エキスポパーク(大阪府吹田市)
    • Related Report
      2013 Research-status Report
  • [Presentation] Ribosomal synthesis of charged N-alkyl amino acid-containing peptides2013

    • Author(s)
      Takashi Kawakami, Toru Sasaki, Patrick C. Reid, Hiroshi Murakami
    • Organizer
      The 4th Asia-Pacific International Peptide Symposium
    • Place of Presentation
      ホテル阪急エキスポパーク(大阪府吹田市)
    • Related Report
      2013 Research-status Report
  • [Presentation] High-Speed In Vitro Selection and Evolution of Functional Polypeptides Using TRAP Display2013

    • Author(s)
      Takahiro Ishizawa, Takashi Kawakami and Hiroshi Murakami
    • Organizer
      The 4th Asia-Pacific International Peptide Symposium
    • Place of Presentation
      ホテル阪急エキスポパーク(大阪府吹田市)
    • Related Report
      2013 Research-status Report
  • [Presentation] 高速試験管内進化法の開発と新規機能性ポリペプチドの探索への応用2013

    • Author(s)
      石沢尭大、川上隆史、村上裕
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド(兵庫県神戸市)
    • Related Report
      2013 Research-status Report
  • [Presentation] 高速試験管内分子進化法を用いた血管内皮増殖因子受容体阻害ペプチドの開発2013

    • Author(s)
      川上隆史、石沢尭大、藤野公茂、菅裕明、村上裕
    • Organizer
      第7回バイオ関連化学シンポジウム
    • Place of Presentation
      名古屋大学豊田講堂(愛知県名古屋市)
    • Related Report
      2013 Research-status Report
  • [Presentation] 高速試験管内進化分子工学法を用いた大規模ペプチドライブラリーの構築2013

    • Author(s)
      石沢尭大、川上隆史、村上裕
    • Organizer
      第7回バイオ関連化学シンポジウム
    • Place of Presentation
      名古屋大学豊田講堂(愛知県名古屋市)
    • Related Report
      2013 Research-status Report
  • [Presentation] 内皮細胞の血管新生を阻害する非天然型環状ペプチドの高速分子進化法による創製2013

    • Author(s)
      川上隆史、石沢尭大、藤野公茂、Patrick C. Reid、菅裕明、村上裕
    • Organizer
      日本ケミカルバイオロジー学会第8回年会
    • Place of Presentation
      東京医科歯科大学M&Dタワー(東京都文京区)
    • Related Report
      2013 Research-status Report
  • [Presentation] 新規機能性ポリペプチドの探索を指向した高速試験管内進化分子工学法の開発2013

    • Author(s)
      石沢尭大、川上隆史、村上裕
    • Organizer
      日本ケミカルバイオロジー学会第8回年会
    • Place of Presentation
      東京医科歯科大学M&Dタワー(東京都文京区)
    • Related Report
      2013 Research-status Report
  • [Book] 進化分子工学 ~高速分子進化によるタンパク質・核酸の開発~2013

    • Author(s)
      石沢尭大、川上隆史、村上裕
    • Publisher
      NTS
    • Related Report
      2013 Research-status Report
  • [Remarks]

    • URL

      http://www.molprof.jp/~kawakami/

    • Related Report
      2015 Annual Research Report
  • [Remarks]

    • URL

      http://researchmap.jp/takakawa/

    • Related Report
      2015 Annual Research Report
  • [Remarks] 川上隆史研究員ホームページ

    • URL

      http://www.molprof.jp/~kawakami/

    • Related Report
      2014 Research-status Report
  • [Remarks] 創薬分子プロファイリング研究センターホームページ

    • URL

      http://www.molprof.jp

    • Related Report
      2014 Research-status Report
  • [Patent(Industrial Property Rights)] 荷電性非タンパク質性アミノ酸含有ペプチドの製造方法2013

    • Inventor(s)
      村上裕、川上隆史、佐々木亨、パトリック・ライド
    • Industrial Property Rights Holder
      村上裕、川上隆史、佐々木亨、パトリック・ライド
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2013-162440
    • Filing Date
      2013-08-05
    • Related Report
      2013 Research-status Report
  • [Patent(Industrial Property Rights)] ペプチドライブラリの製造方法、ペプチドライブラリ、及びスクリーニング方法2013

    • Inventor(s)
      村上裕、川上隆史、佐々木亨、パトリック・ライド
    • Industrial Property Rights Holder
      村上裕、川上隆史、佐々木亨、パトリック・ライド
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2013-100661
    • Filing Date
      2013-05-10
    • Related Report
      2013 Research-status Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi