Non-standard peptide-probe discovery

2013 Fiscal Year Final Research Report

• Project/Area Number: 21000005
• Research Category: Grant-in-Aid for Specially Promoted Research
• Allocation Type: Single-year Grants
• Review Section: Science and Engineering; Chemistry
• Research Institution: The University of Tokyo
• Principal Investigator: SUGA Hiroaki 東京大学, 大学院・理学系研究科, 教授 (00361668)
• Project Period (FY): 2009 – 2013
• Keywords: 天然物有機化学 / 生理活性物質 / 生体高分子 / 生化学 / ケミカルバイオロジー

Research Abstract

This research project aims at developing the genetic code reprogramming technology based on the flexizyme system and expressing natural product-like macrocyclic peptides from mRNA libraries. Moreover, an in vitro display system, referred to RaPID (Random nonstandard Peptide Integrated Discovery) system, has been established to apply for massive screenings of macrocyclic peptides generated by the above technology. This has enabled us to discover molecular probes against various drug targets, leading to a new era of chemical biology.

Research Products

• [Journal Article] One-pot synthesis of azoline-containing peptides in a cell-free translation system integrated with a posttranslational cyclodehydratase SIRT2 (2014)
  • Author(s): Y. Goto, Y. Ito, Y. Kato, S. Tsunoda, H. Suga
  • Journal Title: Chemistry and Biology Volume: (in press)
  • Peer Reviewed
• [Journal Article] An orthogonal ribosome-tRNAs pair via the engineering of peptidyl transferase center (2014)
  • Author(s): N. Terasaka, G. Hayashi1, T. Katoh, and H. Suga
  • Journal Title: Nature Chemical Biology Volume: (in press)
  • Peer Reviewed
• [Journal Article] Selection-based discovery of druglike macrocyclic peptides (2014)
  • Author(s): T. Passioura, T. Katoh, Y. Goto, H. Suga
  • Journal Title: Selection-based discovery of druglike macrocyclic peptides Volume: (in press)
  • Peer Reviewed
• [Journal Article] Protein cocrystallization molecules originating from in vitro selected macrocyclic peptides (2014)
  • Author(s): C.J. Hipolito, N.K. Bashiruddin, H. Suga
  • Journal Title: Current Opinion in Structural Biology Volume: 26 Pages: 24-31
  • DOI: DOI:10.1016/j.sbi.2014.03.001
  • Peer Reviewed
• [Journal Article] Structural basis for gating mechanisms of a eukaryotic P-glycoprotein homolog (2014)
  • Author(s): A. Kodan, T. Yamaguchi, T. Nakatsu, K. Sakiyama, C.J. Hipolito, A. Fujioka, R. Hirokane, K. Ikeguchi, B. Watanabe,J. Hiratake, Y. Kimura, H. Suga, K. Ueda, H. Kato
  • Journal Title: Pro. Nat. Acad. Sci Volume: 111 Pages: 4049-4054
  • Peer Reviewed
• [Journal Article] Structural Basis for Potent Inhibition of SIRT2 Deacetylase by a Macrocyclic Peptide Inducing Dynamic Structural Change (2014)
  • Author(s): K. Yamagata, Y. Goto, H. Nishimasu, J. Morimoto, R. Ishitani, N. Dohmae, N. Takeda, R. Nagai, I. Komuro, H. Suga, O. Nureki
  • Journal Title: Structure Volume: 22 Pages: 345-352
  • Peer Reviewed
• [Journal Article] Flexizymes-facilitated genetic code reprogramming leading to the discovery of drug-like peptides (2014)
  • Author(s): N. Terasaka, H. Suga
  • Journal Title: Chemistry Letters Volume: 43 Pages: 11-19
  • Peer Reviewed
• [Journal Article] Non-standard peptide expression under the genetic code consisting of reprogrammed dual sense codons (2013)
  • Author(s): Y. Goto, M. Iseki, A. Hitomi, H. Murakami, and H. Suga
  • Journal Title: ACS Chemical Biology Volume: 8 Pages: 266, 719
  • DOI: DOI:10.1021/cb400549p
  • Peer Reviewed
• [Journal Article] A macrocyclic peptide that serves as a cocrystallization ligand and inhibits the function of a MATE family transporter (2013)
  • Author(s): C.J. Hipolito, Y. Tanaka, T. Katoh, O. Nureki, H. Suga
  • Journal Title: Molecules Volume: 18 Pages: 10514-10530
  • DOI: DOI:10.3390/molecules180910514
  • Peer Reviewed
• [Journal Article] Structural basis for the drug extrusion mechanism by a MATE multidrug transporter (2013)
  • Author(s): Y. Tanaka, C.J. Hipolito, A.D. Maturana, K. Ito, T. Kuroda, T. Higuchi, T. Katoh, H.E. Kato, M. Hattori, K. Kumazaki, T. Tsukazaki, R. Ishitani, H. Suga, O. Nureki
  • Journal Title: Nature Volume: 496 Pages: 247-251
  • DOI: DOI:10.1002/chem.201300247
  • Peer Reviewed
• [Journal Article] Flexizyme-mediated genetic reprogramming as a tool for noncanonical Peptide synthesis and drug discovery (2013)
  • Author(s): T. Passioura, H. Suga
  • Journal Title: Chemistry European Journal Volume: 19 Pages: 6530-6536
  • DOI: DOI:10.1002/chem.201300247
  • Peer Reviewed
• [Journal Article] In Vitro Selection of Multiple Libraries Created by Genetic Code Reprogramming To Discover Macrocyclic Peptides That Antagonize VEGFR2 Activity in Living Cells (2013)
  • Author(s): T. Kawakami, T. Ishizawa, T. Fujino, P.C. Reid, H. Suga, H. Murakami
  • Journal Title: ACS Chemical Biology Volume: 8 Pages: 1205-1514
  • DOI: DOI:10.1021/cb300697h
  • Peer Reviewed
• [Journal Article] Technologies for the synthesis of mRNA-encoding libraries and discovery of bioactive natural product-inspired non-traditional macrocyclic peptides (2013)
  • Author(s): K. Ito, T. Passioura, H. Suga
  • Journal Title: Molecules Volume: 18 Pages: 3502-3528
  • DOI: DOI:10.3390/molecules18033502
  • Peer Reviewed
• [Journal Article] Reevaluation of the D-amino acid compatibility with the elongation event in translation (2013)
  • Author(s): T. Fujino, Y. Goto, H. Suga, H. Murakami
  • Journal Title: Journal of American Chemical Society Volume: 135 Pages: 1830-1837
  • DOI: DOI:10.1021/ja309570x
  • Peer Reviewed
• [Presentation] 擬天然物の新機能創出分子技術 (2014)
  • Author(s): 菅 裕明
  • Organizer: 日本化学会第94春期年会「社会持続的発展のための分子技術」
  • Place of Presentation: 名古屋大学東山キャンパス(名古屋市)(招待講演)
  • Year and Date: 2014-03-29
• [Presentation] Discovery of natural product-like petides accerelated by RaPID system (2014)
  • Author(s): 菅 裕明
  • Organizer: AsiaTIDES, 2.Plenary Lecture
  • Place of Presentation: シェラトン都ホテル東京(東京都港区)(招待講演)
  • Year and Date: 2014-02-25
• [Presentation] Discovery of natural product-like petides accerelated by RaPID system (2013)
  • Author(s): 菅 裕明
  • Organizer: Solvay Conference of "New Chemistry and New Opportunities from the Expanding Protein Universe"
  • Place of Presentation: International Solvay Institute (Brussels, Belgium)(招待講演)
  • Year and Date: 20131015-19
• [Presentation] Discovery of natural product-like petides accerelated by RaPID system (2013)
  • Author(s): 菅 裕明
  • Organizer: "Jokichi Takamine" 130 years of Glasgow-Japan Collaboration
  • Place of Presentation: University of Glasgow (Glasgow, UK)(招待講演)
  • Year and Date: 20130905-06
• [Presentation] Discovery of natural product-like petides accerelated by RaPID system (2013)
  • Author(s): 菅 裕明
  • Organizer: Current Strategy for Development of Biopharmaceuticals and Small Molecule Drugs
  • Place of Presentation: 北海道大学(北海道札幌)(招待講演)
  • Year and Date: 20130801-02
• [Presentation] Discovery of natural product-like petides accerelated by RaPID system (2013)
  • Author(s): 菅 裕明
  • Organizer: International Conference on Structural Genomics2013, Structural Life Science
  • Place of Presentation: 京王プラザホテル(北海道札幌)(招待講演)
  • Year and Date: 20130729-0801
• [Presentation] Discovery of natural product-like petides accerelated by RaPID system (2013)
  • Author(s): 菅 裕明
  • Organizer: Keynote Lecture Symposium on Chemoselective Reactions for the Synthesis and Application
  • Place of Presentation: Max Planc Institute (Dortmund, Germany)(招待講演)
  • Year and Date: 20130702-05
• [Presentation] Discovery of natural product-like petides accerelated by RaPID system (2013)
  • Author(s): 菅 裕明
  • Organizer: Symposium on Foldamers
  • Place of Presentation: Les Cordeliers Conference Centre(Paris, France)(招待講演)
  • Year and Date: 20130409-12
• [Presentation] Discovery of natural product-like petides accerelated by RaPID system (2013)
  • Author(s): 菅 裕明
  • Organizer: Korean Peptide Protein Society Meeting
  • Place of Presentation: Seoul National University (Seoul, Korea)(招待講演)
  • Year and Date: 2013-11-29
• [Presentation] Discovery of natural product-like petides accerelated by RaPID system (2013)
  • Author(s): 菅 裕明
  • Organizer: Basel Chemical Society Lectureship
  • Place of Presentation: Medicinal Chemistry Navartis Institute (Basel, Switzerland)(招待講演)
  • Year and Date: 2013-10-24
• [Presentation] Discovery of natural product-like petides accerelated by RaPID system (2013)
  • Author(s): 菅 裕明
  • Organizer: RiboClub
  • Place of Presentation: Hotel Cheribourg (Quebec,Canada)(招待講演)
  • Year and Date: 2013-09-22
• [Presentation] Discovery of natural product-like petides accerelated by RaPID system (2013)
  • Author(s): 菅 裕明
  • Organizer: Biochemistry Seminar of University of Colorado BioFrontier Institute
  • Place of Presentation: Univerity of Colorado (Boulder, USA)(招待講演)
  • Year and Date: 2013-09-11
• [Presentation] Discovery of natural product-like petides accerelated by RaPID system (2013)
  • Author(s): 菅 裕明
  • Organizer: Lilly Distinguished Lecturer at Colorado State University
  • Place of Presentation: Colorado State University (Fort Collins, US)(招待講演)
  • Year and Date: 2013-09-10
• [Presentation] Discovery of natural product-like petides accerelated by RaPID system (2013)
  • Author(s): 菅 裕明
  • Organizer: ACS National Meeting
  • Place of Presentation: Indiana Convention Center (Indianapolis, USA)(招待講演)
  • Year and Date: 2013-09-09
• [Presentation] Discovery of natural product-like petides accerelated by RaPID system (2013)
  • Author(s): 菅 裕明
  • Organizer: American Peptide Symposium 2013
  • Place of Presentation: Hilton Waikoloa Village (Hawaii, USA)(招待講演)
  • Year and Date: 2013-06-23
• [Presentation] Discovery of natural product-like petides accerelated by RaPID system (2013)
  • Author(s): 菅 裕明
  • Organizer: Gordon Research Conference, Bioorganic Chemistry
  • Place of Presentation: Proctor Academy (New Hampshire, USA)(招待講演)
  • Year and Date: 2013-06-13
• [Presentation] Discovery of natural product-like petides accerelated by RaPID system (2013)
  • Author(s): 菅 裕明
  • Organizer: 5th Gratama Workshop
  • Place of Presentation: 東京工業大学大岡山キャンパス(東京都目黒区)(招待講演)
  • Year and Date: 2013-05-30
• [Presentation] Discovery of natural product-like petides accerelated by RaPID system (2013)
  • Author(s): 菅 裕明
  • Organizer: RIKEN-Max Planc Joint Symposium
  • Place of Presentation: 理化学研究所和光研究所(埼玉県和光市)(招待講演)
  • Year and Date: 2013-04-16
• [Remarks]
  • URL: http://www.chem.s.u-tokyo.ac.jp/users/biorig/index.html
• [Patent(Industrial Property Rights)] MATE 活性阻害ペプチド (2013)
  • Inventor(s): 菅裕明、濡木理、ヒポリト クリストファー、田中良樹
  • Industrial Property Rights Holder: 東京大学
  • Industrial Property Number: PCT/JP2013, 070779
  • Filing Date: 2013-07-28
  • Overseas
• [Patent(Industrial Property Rights)] 大環状ペプチド、その製造方法、及び大環状ペプチドライブラリを用いるスクリーニング方法 (2013)
  • Inventor(s): 菅裕明
  • Industrial Property Rights Holder: 東京大学
  • Industrial Property Number: 特願2013, 174906
  • Filing Date: 2013-08-26
• [Patent(Industrial Property Rights)] C-Metタンパク質アゴニスト (2013)
  • Inventor(s): 菅裕明、伊藤健一郎
  • Industrial Property Rights Holder: 東京大学
  • Industrial Property Number: 特願-2013, 214771
  • Filing Date: 2013-10-15
• [Patent(Industrial Property Rights)] 安定化された二次構造を有するペプチド、及びペプチドライブラリー、それらの製造方法 (2011)
  • Inventor(s): 菅裕明、樋口岳
  • Industrial Property Rights Holder: 東京大学
  • Industrial Property Number: 特願2012, 546968(JP),13/990123(US), 11845198.8(EP),201180058284.4(CN)
  • Acquisition Date: 2011-12-05
  • Overseas