EVOLUTION/EXPANSION OF GENETIC CODES AND ITS APPLICATION TO PRECISION SEQUENCE CONTROL IN TEMPLATED POLYMERIZATION

• Project/Area Number: 18350084
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Chemistry related to living body
• Research Institution: Kyoto University
• Principal Investigator: AOYAMA Yasuhiro Kyoto University, 大学院・工学研究科, 教授 (00038093)
• Co-Investigator(Kenkyū-buntansha): SANDO Shinsuke 京都大学, 大学院・工学研究科, 助教 (20346084)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,200,000 (Direct Cost: ¥15,200,000、Indirect Cost: ¥3,000,000); Fiscal Year 2008: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2007: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000); Fiscal Year 2006: ¥5,200,000 (Direct Cost: ¥5,200,000)
• Keywords: 翻訳系 / タンパク質生合成 / tRNA / アシルtRNA 合成酵素 / アシル化AMP / リボソーム / EF-Tu / 化学的ミスアシル化AMP / タンパク生合成 / アシルtRNA合成酵素 / mRNA / 遺伝コード / センスコドン / ノンセンスコドン / タンパク翻訳系 / アミノアシルtRNA合成酵素 / アミノ酸 / 非天然アミノ酸 / ヒドロキシカルボン酸 / 終止コドン / ペプチドライブラリー

Research Abstract

非天然基質のタンパク質への導入に関し、リボソームを利用した主鎖伸張型(高)分子合成について検討し、タンパク質のリボソーム合成において適用できる非天然基質としてβ-ヒドロキシ酸が有効な基質になりえることを明らかにした。また、基質についての選択性がEF-Tu との相互作用の強さにあることを解明した。非天然基礎質のタンパク質への導入手法については化学的ミスアシル化AMP 法を開発し、非天然タンパク質の酵素合成に道を拓いた。

Research Products

• [Journal Article] Structure and Function of Molecular Assembly. A Personal Reminiscence (2009)
  • Author(s): Y. Aoyama
  • Journal Title: Bull. CHem. Soc. Jpn 82 Pages: 419-438
  • NAID: 10025117037
  • Peer Reviewed
• [Journal Article] Structure and Function of Molecular Assembly. A Personal Reminiscence (2009)
  • Author(s): Y. Aoyama
  • Journal Title: Bull. Chem. Soc. Jpn. 82 Pages: 419-438
  • NAID: 10025117037
  • Peer Reviewed
• [Journal Article] Synthesis of Puromycin Derivatives with Backbone-Elongated Substrates and Assosiated Translation Inhibitory Activities (2009)
  • Author(s): K. Mizusawa, K. Abe, S. Sando, Y. Aoyama
  • Journal Title: Bioorg. Med. Chem. 17
  • Peer Reviewed
• [Journal Article] Enzymatic N-methylaminoacylation of tRNA Using Chemically Misacylated AMP As a Substrate (2008)
  • Author(s): S. Sando, H. Masu, C. Furutani, Y. Aoyama
  • Journal Title: Org. Biomol. Chem 6 Pages: 2666-2668
  • Peer Reviewed
• [Journal Article] Enzymatic N-methyaminoacylation of tRNA Using Chemically Misacylated AMP as a Substrate (2008)
  • Author(s): S. Sando, H. Masu, C. Furutani, Y. Aoyama
  • Journal Title: Org. Biomol. Chem. 6 Pages: 2666-2668
  • Peer Reviewed
• [Journal Article] Unexpected Preference of the E. coli Translation System for Ester-Bond During Incorporation of Backbone-Elongated Substrates (2007)
  • Author(s): S. Sando, K. Abe, N. Sato, T. Shibata, K. Mizusawa, Y. Aoyama
  • Journal Title: J. Am. Chem. Soc 129 Pages: 6180-6186
  • Peer Reviewed
• [Journal Article] In Vitro Selection of RNA Aptamer Against Escherichia Coli Release Factor 1 (2007)
  • Author(s): S. Sando, A. Ogawa, T. Nishi, M. Hayami, Y. Aoyama
  • Journal Title: Bioorg. Med. Chem. Lett 17 Pages: 1216-1220
  • Peer Reviewed
• [Journal Article] Unexpected preference of the E-Coli translation system for the ester bond during incorporation of backbone-elongated substrates (2007)
  • Author(s): S. Sando, K. Abe, N. Sato, T. Shibata, K. Mizusawa, Y. Aoyama
  • Journal Title: J. Am. Chem. Soc. 129 Pages: 6180-6186
  • Peer Reviewed
• [Journal Article] In vitro selection of RNA aptamer against Escherichiacoli release factor 1 (2007)
  • Author(s): S. Sando, A. Ogawa, T. Nishi, M. Hayami, Y. Aoyama
  • Journal Title: Bioorg. Med. Chem. Lett. 17 Pages: 1216-1220
  • Peer Reviewed
• [Journal Article] Unexpected Preference of the E.col Translation System for the Ester Bond during Incorporation of Backbone-Elongated Substrates (2007)
  • Author(s): S.Sando, K.Abe, N.Sato, T.Shibata, K.Mizusawa, Y.Aoyama
  • Journal Title: J. Am. Chem. Soc. 119(印刷中)
• [Journal Article] In Vitro Selection of RNAAptamers against Escherichia coli Release Factor 1 (2006)
  • Author(s): S. Sando, A. Ogawa, T. Nishi, M. Hayami, Y. Aoyama
  • Journal Title: Bioorg. Med. Chm. Lett 17 Pages: 1216-1220
  • Peer Reviewed
• [Journal Article] Termination-Free Prokaryotic Protein Translation Using Abticodon-Adjusted E. Coli tRNA^<Ser> as Unified Suppressor of the UAA/UGA/UAG Stop Codons. Read-Through Ribosome-Display of Full-Length DHFR with Translated UTR as a Buried Spacer Arm (2006)
  • Author(s): A. Ogawa, S. Sando, Y. Aoyama
  • Journal Title: ChemBioChem 7 Pages: 249-252
  • Peer Reviewed
• [Journal Article] Termination-Free Prokaryotic Protein Translation Using Abticodon-AdjustedE. ColitRNASeras Unified Suppressor of the UAA/UGA/UAG StopCodons. (2006)
  • Author(s): A.Ogawa, S.Sando, Y.Aoyama
  • Journal Title: ChemBioChem 7 Pages: 249-252
• [Journal Article] In Vitro Selection of RNA Aptamers against Escherichia coli Release Factor 1 (2006)
  • Author(s): S.Sando, A.Ogawa, T.Nishi, M.Hayami, Y.Aoyama
  • Journal Title: Bioorg. Med. Chem. Lett. 17 Pages: 1216-1220
• [Journal Article] Synthesis of Puromycin Derivatives with backbone-Elongated Substrates and Associated Translation Inhibitory Activities
  • Author(s): K. zusawa, K. Abe, S. Sando, Y. Aoyama
  • Journal Title: Bioorg. Med. Chem (in press)
  • Peer Reviewed
• [Presentation] A Selex (Artificial Evolution) Approach to "Light-Up" Dye-Binding Macromolecular Host for Bioimaging (2008)
  • Author(s): Y. Aoyama
  • Organizer: 3th International Symposium on Macrocyclic and Supramolecular Chemistry
  • Place of Presentation: Las Vegas (USA)
  • Year and Date: 2008-07-13
• [Presentation] リボソームを利用した非天然型高分子合成に向けた化学的アプローチ : 化学的ミスアシル化AMP 法に基づく非天然基質の触媒的tRNA 付加反応と翻訳系への展開 (2008)
  • Author(s): 山東信介・益啓貴・青山安宏
  • Organizer: 日本化学会第88春季年会
  • Place of Presentation: 立教大学、船橋、千葉
  • Year and Date: 2008-03-29
• [Presentation] 化学的アプローチに基づく生体分子機能の拡張と非侵襲的解析ツールへの展開 (2007)
  • Author(s): 山東信介・青山安宏
  • Organizer: 第2回無細胞生命科学研究会
  • Place of Presentation: 東京大学、東京
  • Year and Date: 2007-10-19
• [Presentation] 非天然分子を基質とする触媒的tRNAミスアシル化に向けたアプローチ : 化学的ミスアシル化AMP 法の検討 (2007)
  • Author(s): 益啓貴・山東信介・青山安宏
  • Organizer: 第22回生体機能関連化学シンポジウム
  • Place of Presentation: 東北大学、仙台、宮城
  • Year and Date: 2007-09-28
• [Presentation] A new strategy for acylation of tRNA with unnatural substrates (2007)
  • Author(s): Hiroki Masu, Masayoshi Hayami, Shinsuke Sando, , Yasuhiro Aoyama
  • Organizer: 134th ACS National Meeting
  • Place of Presentation: Boston, USA
  • Year and Date: 2007-08-22
• [Presentation] Rational design of main-chain elongated substrates acceptable by the E.coli ribosome (2007)
  • Author(s): Keigo Mizusawa, Shinsuke Sando, , Yasuhiro Aoyama
  • Organizer: 134th ACS National Meeting
  • Place of Presentation: Boston (USA)
  • Year and Date: 2007-08-22
• [Presentation] A New Strategy for Enzymatic Acylation of tRNA with Unnatural Substrates. (2007)
  • Author(s): H. Masu, S. Sando, Y. Aoyama
  • Organizer: American Chemical Society 234th National Meeting & Exposition
  • Place of Presentation: ボストン(米国)
  • Year and Date: 2007-08-22
• [Presentation] 大腸菌リボソームによって導入可能な非天然基質の拡張 : 主鎖伸長型基質の導入に関与するファクター (2007)
  • Author(s): 水澤圭吾・阿部健二・山東信介・青山安宏
  • Organizer: 日本ケミカルバイオロジー研究会第1回年会
  • Place of Presentation: 京都大学、京都
  • Year and Date: 2007-05-09
• [Presentation] 蛋白質翻訳システムの応用に向けた化学的アプローチ (2007)
  • Author(s): 益啓貴・速水将勝・小川敦司・西輝之・山東信介・青山安宏
  • Organizer: 日本ケミカルバイオロジー研究会第1回年会
  • Place of Presentation: 京都大学、京都
  • Year and Date: 2007-05-09
• [Presentation] 蛋白質翻訳システムの応用に向けた化学的アプローチ (2007)
  • Author(s): 益啓貴・速水将勝・小川敦司・西輝之・山東信介・青山安宏
  • Organizer: 日本化学会第87春季年会
  • Place of Presentation: 関西大学、吹田、大阪
  • Year and Date: 2007-03-26
• [Presentation] 大腸菌リボソームによって導入可能な非天然基質の合理的拡張 : 主鎖伸長型基質の導入に関与するファクター (2007)
  • Author(s): 水澤圭吾・阿部健二・山東信介・青山安宏
  • Organizer: 日本化学会第87春季年会
  • Place of Presentation: 関西大学、吹田、大阪
  • Year and Date: 2007-03-25
• [Presentation] Effort toward Ribosome-Catalyzed Synthesis of Structurally-Diverse Peptidomimetic Libraries : Expansion of Unnatural Substrates Acceptable by the E. coli Ribosome (2006)
  • Author(s): Kenji Abe, Nobuhiko Sato, Toshihiro Shibata, Keigo Mizusawa, , Shinsuke Sando, Yasuhiro Aoyama
  • Organizer: International Conference of Japanese Peptide Symposium/Peptide Engineering Meeting
  • Place of Presentation: 横浜、神奈川
  • Year and Date: 2006-11-05
• [Remarks] 本研究成果を含む業績により山東信介は平成20年度日本化学会進歩賞を受賞した。また、学会発表(1)および(11)はそれぞれの学会に置いてポスター賞を受賞した。
  • URL: http://www.sbchem.kyoto-u.ac.jp/aoyama-lab/