Development of a synthetic method of modified histone aiming at elucidation of the molecular mechanism of the gene expression regulation

• Project/Area Number: 18310145
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Living organism molecular science
• Research Institution: Osaka University
• Principal Investigator: AIMOTO Saburo Osaka University, 蛋白質研究所, 教授 (80029967)
• Co-Investigator(Kenkyū-buntansha): TAJIMA Shoji 大阪大学, 蛋白質研究所, 教授 (50132931) ; KAWAKAMI Toru 大阪大学, 蛋白質研究所, 准教授 (70273711) ; SUETAKE Isao 大阪大学, 蛋白質研究所, 准教授 (80304054)
• Project Period (FY): 2006 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥19,310,000 (Direct Cost: ¥15,800,000、Indirect Cost: ¥3,510,000); Fiscal Year 2009: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2008: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2007: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2006: ¥4,100,000 (Direct Cost: ¥4,100,000)
• Keywords: ヒストン / メチル化 / 化学合成 / 翻訳後修飾 / 遺伝子発現 / メチル化リシン / ヒストンH3 / ライゲーション法 / ライブラリー / ライゲ-ション法

Research Abstract

To establish synthetic methods of histone H3 tail and modified histone H3, we searched methods for modified lysine synthesis, chemical synthesis of modified lysine-containing histone H3 tails, and chemical synthesis of full sequence histone H3. Synthetic modified histone H3 tails contributed to the biochemical elucidation of polycomb repressive complex 2. 9Lys(Me_3)-histone H3 was also synthezised.

Research Products

• [Journal Article] Formation of Peptide Thioesters by an N to S Acyl Shift Reaction at the Cysteinyl Prolyl Cysteine Position (2010)
  • Author(s): Sakiko Shimizu, Saburo Aimoto, Toru Kawakami
  • Journal Title: Peptide Science 2009 Pages: 153-154
  • Peer Reviewed
• [Journal Article] Synthesis of Peptide Thioesters Based on an N to S Acyl Shift Reaction (2010)
  • Author(s): Toru Kawakami, Sakiko Shimizu, Saburo Aimoto
  • Journal Title: Peptide Science 2009 Pages: 79-80
  • Peer Reviewed
• [Journal Article] Formation of Peptide Thioesters by an N to S Acyl Shift Reaction at the Cysteinyl Prolyl Cysteine Position (2010)
  • Author(s): S.Shimizu
  • Journal Title: Peptide Science 2009 (In press)
  • Peer Reviewed
• [Journal Article] Synthesis of Peptide Thioesters Based on an N to S Acyl Shift Reaction (2010)
  • Author(s): T.Kawakami
  • Journal Title: Peptide Science 2009 (In press)
  • Peer Reviewed
• [Journal Article] Synthesis of Peptide Thioester, by the Cysteinyl Prolyl Ester (CPE) Method (2009)
  • Author(s): Toru Kawakami, Saburo Aimoto
  • Journal Title: Peptide Science 2008 Pages: 171-172
  • NAID: 10027166150
  • Peer Reviewed
• [Journal Article] 2-Nitrobenzylcarbamate-type Photocleavable Linker Having Fmoc-aminoalkyloxy Group: Preparation and Application to Peptide Purification (2009)
  • Author(s): Toshiaki Hara, Akira Tainosho, Toru Kawakami, Saburo Aimoto
  • Journal Title: Peptide Science 2008 Pages: 199-201
  • NAID: 10027166207
  • Peer Reviewed
• [Journal Article] Methylthio Groups for Thiol Protection that realize the Sequential Ligation by Native Chemical Ligation followed by Thioester method (2009)
  • Author(s): Yuichi Akai, Lisa Takemura, Yuko Aoki, Masazumi Waseda, Toru Kawakami, Saburo Aimoto
  • Journal Title: Peptide Science 2008 Pages: 201-201
  • NAID: 10027166211
  • Peer Reviewed
• [Journal Article] Peptide Purification Using The Selective Reaction Between Aminooxy Group and Isothiocyanate Group (2009)
  • Author(s): Akira Tainosho, Toshiaki Hara, Ken'ichiro Nakamura, Toru Kawakami, Saburo Aimoto
  • Journal Title: Peptide Science 2008 Pages: 205-207
  • Peer Reviewed
• [Journal Article] Synthesis of peptide thioesters via an N-S acyl shift reaction under mild acidic conditions using an N-4, 5-dimethoxy-2-mercaptobenzyl auxiliary group (2009)
  • Author(s): Ken'ichiro Nakamura, Tomoki Kanao, Tomoya Uesugi, Toshiaki Hara, Takeshi Sato, Toru Kawakami, Saburo Aimoto
  • Journal Title: J. Peptide Sci 15 Pages: 731-7
  • Peer Reviewed
• [Journal Article] Peptide purification by affinity chromatography based on a-ketoacyl group chemistry (2009)
  • Author(s): Toshiaki Hara, Akira Tainosho, Ken'ichiroh Nakamura, Takeshi Sato, Toru Kawakami, Saburo Aimoto
  • Journal Title: J. Peptide Sci 15 Pages: 369-376
  • Peer Reviewed
• [Journal Article] The Use of a Cysteinyl Prolyl Ester (CPE) Autoactivating Unit in Peptide Ligation Reactions (2009)
  • Author(s): Toru Kawakami, Saburo Aimoto
  • Journal Title: Tetrahedron 65 Pages: 3871-3877
  • Peer Reviewed
• [Journal Article] Synthesis of peptide thioesters via an N-S acyl shift reaction under mild acidic conditions using an N-4, 5-dimethoxy-2-mercaptobenzyl auxiliary group (2009)
  • Author(s): K.Nakamura
  • Journal Title: J.Peptide Science 15 Pages: 731-7
  • Peer Reviewed
• [Journal Article] Peptide purification by affinity chromatography based on α-ketoacyl group chemistry (2009)
  • Author(s): Toshiaki Hara, Akira Tainosho, Ken'ichiroh Nakamura, Takeshi Sato, Toru Kawakami, Saburo Aimoto
  • Journal Title: J. Peptide Sci. 15 Pages: 369-376
  • Peer Reviewed
• [Journal Article] Peptide purification by affinity chromatography based on α -ketoacyl group chemistry (2009)
  • Author(s): T. Hara
  • Journal Title: Journal of Peptide Science (In press)
  • Peer Reviewed
• [Journal Article] 2-Nitrobenzylcarbamate-type Photocleavable Linker Having Fmoc-amino alkyloxy Group : Preparation and Application to Peptide Purification (2009)
  • Author(s): T. Hara
  • Journal Title: Peptide Science 2008 (In press)
  • Peer Reviewed
• [Journal Article] Peptide Purification Using The Selective Reaction Between Aminooxy Group and Isothiocyanate Group, Followed by Edman Degradation. (2009)
  • Author(s): A. Tainosho
  • Journal Title: Peptide Science 2008 (In press)
  • Peer Reviewed
• [Journal Article] The Use of a Cysteinyl Prolyl Ester (CPE) Autoactivating Unit in Peptide Ligation Reactions (2009)
  • Author(s): T. Kawakami
  • Journal Title: Tetrahedron (In press)
  • Peer Reviewed
• [Journal Article] Synthesis of a Partial Sequence of Site- (2008)
  • Author(s): Hisao Fujimoto, Chieko Kita, Akira Tainosho, Yuichi Akai, Lisa Takemura, Hitomi Kanda, Toru, Kawakami, Saburo Aimoto
  • Journal Title: Specifically Methylated Histone H3 Peptide Science 2007 Pages: 209-210
  • Peer Reviewed
• [Journal Article] Synthesis of a Partial Sequence of Site-Specifically Methylated Histone H3 (2008)
  • Author(s): H. Fujimoto
  • Journal Title: Peptide Science 2007 Pages: 209-210
  • Peer Reviewed
• [Journal Article] Peptide Thioester Synthesis via an Auxiliary-Mediated N-S Acyl Shift Reaction in SolutionInt (2007)
  • Author(s): Ken'ichiro Nakamura, Hiroaki Mori, Toru Kawakami, Hironobi Hojo, Yoshiaki Nakahara, Saburo Aimoto
  • Journal Title: J. Peptide Res. Therapeutics 13 Pages: 191-202
  • Peer Reviewed
• [Journal Article] Sequential Peptide Ligation by Using a Controlled Cysteinyl Prolyl Ester (CPE) Autoactivating Unit (2007)
  • Author(s): Toru Kawakami, Saburo Aimoto
  • Journal Title: Tetrahedron Lett 48 Pages: 1903-1905
  • Peer Reviewed
• [Journal Article] Polypeptide Synthesis via the N-to S-Acyl Shift Reaction (2007)
  • Author(s): Toru Kawakami, Ken'ichiro Nakamura, Saburo Aimoto
  • Journal Title: Peptides 2006 Pages: 198-199
  • Peer Reviewed
• [Journal Article] Peptide Ligation Using a Building Block Having a Cysteinyl Prolyl Ester (CPE) Autoactivating Unit at the Carboxy Terminus (2007)
  • Author(s): Toru Kawakami, Saburo Aimoto
  • Journal Title: Chem. Lett 36 Pages: 76-77
  • NAID: 10018663050
  • Peer Reviewed
• [Journal Article] Sequential Peptide Ligation by Using a Controlled Cysteinyl Prolyl Ester (CPE) Autoactivating Unit (2007)
  • Author(s): Toru Kawakami, Saburo Aimoto
  • Journal Title: Tetrahedron Lett. 48 Pages: 1903-1905
  • Peer Reviewed
• [Journal Article] Peptide Ligation Using a Building Block Having a Cysteinyl Prolyl Ester (CPE) Autoactivating Unit at the Carboxy Terminus (2007)
  • Author(s): Toru Kawakami, Saburo Aimoto
  • Journal Title: Chem. Lett. 36 Pages: 76-77
  • NAID: 10018663050
  • Peer Reviewed
• [Journal Article] Sequential peptide ligation by using a controlled cysteinyl prolyl ester (CPE) autoactivating unit. (2007)
  • Author(s): T. Kawakami
  • Journal Title: Tetrahedron Lett. 48 Pages: 1903-1905
  • Peer Reviewed
• [Journal Article] Polypeptide Synthesis via the N-to S-Acyl Shift Reaction (2007)
  • Author(s): T. Kawakami
  • Journal Title: Peptides 2006 Pages: 198-199
  • Peer Reviewed
• [Journal Article] Peptide ligation thinvolves an intramolecular N to S acyl shift reaction (2006)
  • Author(s): Toru Kawakami, Ken'ichiro Nakamura, Saburo Aimoto
  • Journal Title: Peptide Science 2006 29
• [Journal Article] N-S acyl shift reaction on peptide backbone and its application to preparation of peptide thioesters (2006)
  • Author(s): Ken'ichiro Nakamura, Toru Kawakami, Hironobu Hojo, Yoshiaki Nakahara, Saburo Aimoto
  • Journal Title: Peptide Science 2006 42
  • NAID: 10020528860
• [Presentation] 2-ニトロベンジルカルバメイト型光分解リンカーを用いる化学合成ペプチドの精製 (2010)
  • Author(s): 原利明、田結荘明、川上徹、相本三郎
  • Organizer: 日本化学会第90回春季年会
  • Place of Presentation: 近畿大学、東大阪市
  • Year and Date: 2010-03-27
• [Presentation] Cys-Pro-Cys部位におけるN-Sアシル基転位反応を利用したペプチドチオエステルの合成 (2010)
  • Author(s): 清水咲子、相本三郎、川上徹
  • Organizer: 日本化学会第90回春季年会
  • Place of Presentation: 近畿大学、東大阪市
  • Year and Date: 2010-03-27
• [Presentation] Cys-Pro-Cys部位におけるN-5アシル基転位反応を利用したペプチドチオエステルの合成 (2010)
  • Author(s): 清水咲子
  • Organizer: 日本化学会第90回春季年会
  • Place of Presentation: 近畿大学、東大阪市
  • Year and Date: 2010-03-27
• [Presentation] Histone H3K9 trimethylation stimulates the histone H3K27 methylation activity of PRC2 bypassing Eed (2010)
  • Author(s): Isao Suetake, Saburo Aimoto, Yuko Aoki, Kyoichi Isono, Toru Kawakami, Hiroshi Kimura, Akihiko Koseki, Yuichi Mishima; Osamu Nishimura, Shoji Tajima, Makoto Watanabe
  • Organizer: Keystone symposium
  • Place of Presentation: Sagebrush Inn and Conference Center, Taos, New Mexico
  • Year and Date: 2010-01-20
• [Presentation] Synthesis of Peptide Thioesters Based on an N to S Acyl Shift Reaction (2009)
  • Author(s): Toru Kawakami, Sakiko Shimizu, Saburo Aimoto
  • Organizer: 第46回ペプチド討論会
  • Place of Presentation: 北九州国際会議場、北九州市
  • Year and Date: 2009-11-05
• [Presentation] Formation of Peptide Thioesters by an N to S Acyl Shift Reaction at the Cysteinyl Prolyl Cysteine Position (2009)
  • Author(s): Sakiko Shimizu, Saburo Aimoto, Toru Kawakami
  • Organizer: 第46回ペプチド討論会
  • Place of Presentation: 北九州国際会議場、北九州市
  • Year and Date: 2009-11-05
• [Presentation] ポリコーム群蛋白質複合体PRC2によるH3K27メチル化の新たな活性調節機構 (2009)
  • Author(s): 三島優一、磯野協一、青木優子、川上徹、渡辺真、木村宏、西村紀、相本三郎、古関明彦、田嶋正二、末武勲
  • Organizer: 第82回日本生化学会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2009-10-23
• [Presentation] ボリコーム群蛋白質複合体PRC2によるH3K27メチル化の新たな活性調節機構 (2009)
  • Author(s): 三島優一
  • Organizer: 第82回 日本生化学会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2009-10-23
• [Presentation] メチルチオ基をチオール保護基として用いるネイティブケミカルライゲーション法とチオエステル法による連続ライゲーション法 (2009)
  • Author(s): 赤井優一、早稲田真澄、青木優子、竹村梨沙、川上徹、相本三郎
  • Organizer: 日本化学会第89春季年会
  • Place of Presentation: 千葉
  • Year and Date: 2009-03-29
• [Presentation] アミノオキシ基とイソチオシアネート基の選択的化学反応とそれに続くエドマン分解を利用したペプチドの精製 (2008)
  • Author(s): 田結荘明、原利明、中村健一郎、川上徹、相本三郎
  • Organizer: 第45回ペプチド討論会
  • Place of Presentation: 東京
  • Year and Date: 2008-10-30
• [Presentation] ネイティブケミカルライゲーション法とチオエステル法の併用を可能にするチオール保護基としてのメチルチオ基の利用 (2008)
  • Author(s): 赤井優一、竹村梨沙、青木優子、早稲田真澄、川上徹、相本三郎
  • Organizer: 第45回ペプチド討論会
  • Place of Presentation: 東京
  • Year and Date: 2008-10-30
• [Presentation] Synthesis of Peptide Thioester by the Cysteinyl Prolyl Ester (CPE) Method (2008)
  • Author(s): Toru Kawakami, Saburo Aimoto
  • Organizer: 第45回ペプチド討論会
  • Place of Presentation: 東京
  • Year and Date: 2008-10-30
• [Presentation] Fmoc-アミノプロピルオキシ基を導入した2-ニトロベンジルカルバメイト型リンカーの合成とペプチド精製への応用 (2008)
  • Author(s): 原利明、田結荘明、川上徹、相本三郎
  • Organizer: 第45回ペプチド討論会
  • Place of Presentation: 東京
  • Year and Date: 2008-10-29
• [Presentation] Peptide thioester preparation and peptide ligation using cysteinyl prolyl ester (CPE) autoactivating unit (2008)
  • Author(s): T o ru Ka wak ami, Sab uro A imo to
  • Organizer: 30 th Eu rop ean P ept ide Symposium
  • Place of Presentation: ヘルシンキ
  • Year and Date: 2008-09-01
• [Presentation] Peptide thioester preparation and peptide ligation using cysteinyl prolyl ester (CPE) autoactivating unit (2008)
  • Author(s): Toru Kawakami
  • Organizer: 3oth European Peptide Symposium
  • Place of Presentation: ヘルシンキ
  • Year and Date: 2008-09-01
• [Presentation] ペプチドCys-Proエステルを合成ブロックとして用いるトリメチルリシン含有ヒストンH3合成法の研究 (2008)
  • Author(s): 赤井優一、藤本久雄、竹村梨沙、田結荘明、喜多知恵子、神田仁美、川上徹、相本三郎
  • Organizer: 日本化学会第88春季年会
  • Place of Presentation: 東京
  • Year and Date: 2008-03-27
• [Presentation] α-ケトアシル基の形成と切断を鍵反応とするペプチド精製法の開発 (2008)
  • Author(s): 原利明、田結荘明、藤本大樹、川上徹、相本三郎
  • Organizer: 日本化学会第88春季年会
  • Place of Presentation: 東京
  • Year and Date: 2008-03-27
• [Presentation] ペプチドCys-Proエステルを合成ブロックとして用いるトリメチルリシン含有ヒストンH3合成法の研究 (2008)
  • Author(s): 赤井 優一, 他
  • Organizer: 日本化学会第88春季年会
  • Place of Presentation: 東京池袋
  • Year and Date: 2008-03-27
• [Presentation] ベプチドCys-Proエステルを合成ブロックとして用いるトリメチルリシン含有ヒストンH3合成法の研究 (2008)
  • Author(s): 赤井 優一
  • Organizer: 日本化学会第88春季年会
  • Place of Presentation: 東京
  • Year and Date: 2008-03-27
• [Presentation] ペプチドCys-Proエステルを合成ブロックとして用いるトリメチルリシン含有ヒストンH3 合成法の研究 (2008)
  • Author(s): 赤井優一
  • Organizer: 日本化学会第88春季年会
  • Place of Presentation: 東京都
  • Year and Date: 2008-03-27
• [Presentation] 部位特異的に修飾されたヒストンH3部分配列の合成 (2007)
  • Author(s): 藤本久雄、喜多千恵子、田結荘明、赤井優一、竹村梨沙、神田仁美、川上徹、相本三郎
  • Organizer: 第44回ペプチド討論会
  • Place of Presentation: 富山市
  • Year and Date: 2007-11-08
• [Presentation] N to S Acyl Shift Reaction in Peptide Ligation (2007)
  • Author(s): Toru Kawakami, Ken'ichiroh Nakamura, Hisao Fujimoto, Saburo Aimoto
  • Organizer: 4th international Peptide Symposium
  • Place of Presentation: ーストラリア・ケアンズ
  • Year and Date: 2007-10-23
• [Presentation] N to S Acyl Shift Reaction in Peptide Ligation (2007)
  • Author(s): T. Kawakami
  • Organizer: 4th international Peptide Symposium
  • Place of Presentation: オーストラリア・ケアンズ
  • Year and Date: 2007-10-23
• [Presentation] PEPTIDE THIOESTER SYNTHESIS BY AN ON-RESIN AUXILIARY-MEDIATED N-S ACYL SHIFT REACTION (2007)
  • Author(s): Saburo Aimoto
  • Organizer: Modern Solid Phase Peptide Synthesis, Its Applications
  • Place of Presentation: オーストラリア・ポートダグラス
  • Year and Date: 2007-10-19
• [Presentation] PEPTIDE THIOESTER SYNTHESIS BY AN ON-RESINAUXILIARY-MEDIATED N-S ACYL SHIFT REACTION (2007)
  • Author(s): S. Aimoto
  • Organizer: Modern Solid Phase Peptide Synthesis & Its Applications
  • Place of Presentation: オーストラリア・ポートダグラス
  • Year and Date: 2007-10-19
• [Presentation] Peptide Ligation via the N to S Acyl Shift Reaction (2007)
  • Author(s): oru Kawakami, Saburo Aimoto
  • Organizer: Chemical Protein Synthesis Meeting
  • Place of Presentation: オーストラリア・ヘロン島
  • Year and Date: 2007-10-18
• [Presentation] Peptide Ligation via the In-Situ Transformation of an Amide into a Thioester at a Cysteine Residue (2007)
  • Author(s): Toru Kawakami, Saburo Aimoto
  • Organizer: 20th American Peptide Society Symposium
  • Place of Presentation: カナダ・モントリオール
  • Year and Date: 2007-06-27
• [Remarks]
  • URL: http://www.protein.osaka-u.ac.jp/organic/index.html
• [Remarks]
  • URL: http://www.protein.osaka-u.ac.jp/organic/index.html
• [Remarks]
  • URL: http://www.protein.osaka-u.ac.jp/organic/index.html