Action mechanism study of PF1171 hexapeptides focused on their 3D structures

• Project/Area Number: 26850068
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Bioorganic chemistry
• Research Institution: Mie University (2015-2016); Tohoku University (2014)
• Principal Investigator: MASUDA Yuichi 三重大学, 生物資源学研究科, 准教授 (90617755)
• Co-Investigator(Renkei-kenkyūsha): KAI Kenji 大阪府立大学, 大学院生命環境科学研究科, 講師 (40508404)
• Research Collaborator: TANAKA Ren 東北大学, 大学院薬学研究科, 大学院生
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 環状ペプチド / カイコ / アポリポタンパク質B / X線結晶構造解析 / 核磁気共鳴 / 三次元構造 / 構造活性相関 / 分子プローブ / 有機化学 / 立体配座 / NMR / 光親和性標識 / 構造－活性相関 / 固相合成 / コンホメーション

Outline of Final Research Achievements

We achieved organic synthesis of PF1171 hexapeptides, cyclic peptides with paralytic activity against silkworms and inhibitory activity against production of apolipoprotein B. X-ray crystallography and nuclear magnetic resonance revealed significance of intramolecular hydrogen bonds in maintaining 3D structure of PF1171 hexapeptides. 3D structure-activity relationship study suggested that the 3D structure observed in the crystal is closely related to bioactivity. Based on the structure-activity relationship, we designed and synthesized molecular probes of PF1171 hexapeptides which can search for their target biomolecules.

Research Products

• [Int'l Joint Research] University of East Anglia(英国)
• [Journal Article] Design, Synthesis, and Biological Evaluation of Beauveriolide Analogues Bearing Photoreactive Amino Acids (2016)
  • Author(s): Masuda Y, Aoyama K, Yoshida M, Kobayashi K, Ohshiro T, Tomoda H, Doi T.
  • Journal Title: Chemical and Pharmaceutical Bulletin Volume: 64 Issue: 7 Pages: 754-765
  • DOI: 10.1248/cpb.c16-00095
  • NAID: 130005160040
  • ISSN: 0009-2363, 1347-5223
  • Peer Reviewed / Open Access
• [Journal Article] Synthesis of (2S,3R,4R)-3,4-dihydroxyarginine and its inhibitory activity against nitric oxide synthase. (2016)
  • Author(s): Masuda, Y., Maruyama, C., Kawabata, K., Hamano, Y., Doi, T.
  • Journal Title: Tetrahedron Volume: 72 Issue: 36 Pages: 5602-5611
  • DOI: 10.1016/j.tet.2016.07.050
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 化学工業 (2016)
  • Author(s): 増田裕一，土井隆行
  • Journal Title: 生物活性環状ペプチドPF1171類とapratoxin Cの全合成と三次元構造解析 Volume: 67 Pages: 18-25
  • Acknowledgement Compliant
• [Journal Article] Potent oxazoline analogue of apratoxin C: synthesis, biological evaluation, and conformational analysis. (2016)
  • Author(s): Yoshida, M., Onda, Y., Masuda, Y., Doi, T.
  • Journal Title: Biopolymers (Peptide Science) Volume: 未定 Issue: 4 Pages: 404-414
  • DOI: 10.1002/bip.22781
  • Peer Reviewed / Open Access
• [Journal Article] Structure revision of similanamide to PF1171C by total synthesis. (2015)
  • Author(s): Masuda, Y., Tanaka, R., Ganesan, A., Doi, T.
  • Journal Title: J. Nat. Prod. Volume: 78 Issue: 9 Pages: 2286-2291
  • DOI: 10.1021/acs.jnatprod.5b00643
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Foxo3a Inhibitors of Microbial Origin, JBIR-141 and JBIR-142 (2015)
  • Author(s): Teppei Kawahara, Noritaka Kagaya, Yuichi Masuda, Takayuki Doi, Miho Izumikawa, Kumiko Ohta, Atsushi Hirao, Kazuo Shin-ya
  • Journal Title: Organic letters Volume: 17 Issue: 21 Pages: 5476-5479
  • DOI: 10.1021/acs.orglett.5b02842
  • Peer Reviewed / Open Access
• [Journal Article] Total synthesis and biological evaluation of PF1171A, C, F, and G, cyclic hexapeptides with insecticidal activity (2014)
  • Author(s): Masuda, Y., Tanaka, R., Kai, K., Ganesan, A., Doi, T.
  • Journal Title: J. Org. Chem. Volume: 79 Issue: 17 Pages: 7844-7853
  • DOI: 10.1021/jo500861k
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Total Synthesis and Conformational Analysis of Apratoxin C (2014)
  • Author(s): Y. Masuda, J. Suzuki, Y. Onda, Y. Fujino, M. Yoshida, T. Doi
  • Journal Title: The Journal of Organic Chemistry Volume: 79 Issue: 17 Pages: 8000-8009
  • DOI: 10.1021/jo501130b
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] (2S,3R,4R)-3,4-dihydroxyarginineの合成と一酸化窒素合成酵素の阻害活性 (2017)
  • Author(s): 増田 裕一，丸山 千登勢，川畑 球一，濱野 吉十，土井 隆行
  • Organizer: 日本農芸化学会2017年度大会
  • Place of Presentation: 京都女子大学（京都府京都市）
  • Year and Date: 2017-03-17
• [Presentation] 環状ペプチドの三次元構造に着目した構造－活性相関研究 (2016)
  • Author(s): 増田 裕一
  • Organizer: 第51回 天然物化学談話会
  • Place of Presentation: 湯沢東映ホテル（新潟県南魚沼郡）
  • Year and Date: 2016-07-06
• [Presentation] カイコ麻痺活性を示す環状ペプチドPF1171類の三次元構造－活性相関 (2016)
  • Author(s): 増田裕一，田中錬，土井隆行
  • Organizer: 日本農芸化学会2016年度大会
  • Place of Presentation: 札幌コンベンションセンター，札幌
  • Year and Date: 2016-03-27
• [Presentation] Total synthesis and 3D structural analysis of apratoxin C (2015)
  • Author(s): Yuichi Masuda, Jun Suzuki, Masahito Yoshida, Takayuki Doi
  • Organizer: International Chemical Congress of Pacific Basin Societies 2015 (PACIFICHEM 2015)
  • Place of Presentation: Honolulu, Hawaii
  • Year and Date: 2015-12-15
  • Int'l Joint Research
• [Presentation] Synthetic study of Asperterrestide A, a cytotoxic cyclic tetrapeptide (2015)
  • Author(s): Yuichi Masuda, Zhang Linnan, Takayuki Doi
  • Organizer: Pharmaceutical Science Symposium 2015 in Sendai
  • Place of Presentation: Sakura Hall in Tohoku University, Sendai
  • Year and Date: 2015-11-16
  • Int'l Joint Research
• [Presentation] 分子プローブを指向したPF1171F類縁体の合成と生物活性評価 (2015)
  • Author(s): 増田裕一，田中錬，土井隆行
  • Organizer: 第54回 日本薬学会東北支部大会
  • Place of Presentation: 岩手医科大学矢巾キャンパス，岩手
  • Year and Date: 2015-09-26
• [Presentation] Synthetic study for asperterrestide A (2015)
  • Author(s): 増田裕一，張 林楠，土井隆行
  • Organizer: 第54回 日本薬学会東北支部大会
  • Place of Presentation: 岩手医科大学矢巾キャンパス，岩手
  • Year and Date: 2015-09-26
• [Presentation] 立体化学の解明を目指した4-hydroxycapreomycidineの全合成研究 (2015)
  • Author(s): 増田裕一，森田大貴，土井隆行
  • Organizer: 第54回 日本薬学会東北支部大会
  • Place of Presentation: 岩手医科大学矢巾キャンパス，岩手
  • Year and Date: 2015-09-26
• [Presentation] カイコ麻痺活性を示す環状ペプチドPF1171類の全合成と三次元構造－活性相関 (2015)
  • Author(s): 増田裕一，田中錬，土井隆行
  • Organizer: 第57回 天然有機化合物討論会
  • Place of Presentation: 神奈川県民ホール，横浜
  • Year and Date: 2015-09-09
• [Presentation] Synthetic Study of Asperterrestide A (2015)
  • Author(s): Yuichi Masuda, Linnan Zhang, Takayuki Doi
  • Organizer: Tohoku University's Chemistry Summer School 2015
  • Place of Presentation: Tohoku University, Sendai
  • Year and Date: 2015-08-27
  • Int'l Joint Research
• [Presentation] 生物活性環状ペプチドPF1171類の構造活性相関研究 (2015)
  • Author(s): 増田裕一，田中錬，土井隆行
  • Organizer: 日本ケミカルバイオロジー学会 第10回年会
  • Place of Presentation: 東北大学萩ホール，仙台
  • Year and Date: 2015-06-10
• [Presentation] 昆虫麻痺活性を示す環状ペプチドPF1171類の全合成と三次元構造解析 (2015)
  • Author(s): 増田裕一，田中錬，甲斐健次，A. Ganesan, 土井隆行
  • Organizer: 日本農芸化学会2015年度大会
  • Place of Presentation: 岡山大学，岡山
  • Year and Date: 2015-03-26 – 2015-03-29
• [Presentation] 4-OH capreomycidine の全合成 (2015)
  • Author(s): 森田大貴，増田裕一，土井隆行
  • Organizer: 日本薬学会第135年会
  • Place of Presentation: 神戸学院大学，兵庫
  • Year and Date: 2015-03-25 – 2015-03-28
• [Presentation] Total synthesis and 3D structural analysis of PF1171A, C, F, and G (2014)
  • Author(s): Yuichi Masuda, Ren Tanaka, Kenji Kai, A. Ganesan, and Takayuki Doi
  • Organizer: 第51回ペプチド討論会
  • Place of Presentation: 徳島大学蔵本キャンパス 大塚講堂，徳島
  • Year and Date: 2014-10-22 – 2014-10-24
• [Presentation] Synthesis and biological evaluation of PF1171F analogues (2014)
  • Author(s): Yuichi Masuda, Ren Tanaka, Kenji Kai, A. Ganesan, and Takayuki Doi
  • Organizer: 第51回ペプチド討論会
  • Place of Presentation: 徳島大学蔵本キャンパス 大塚講堂，徳島
  • Year and Date: 2014-10-22 – 2014-10-24
• [Presentation] Apratoxin C オキサゾリン誘導体の全合成 (2014)
  • Author(s): 恩田勇一，鈴木淳，吉田将人，増田裕一，土井隆行
  • Organizer: 第53回日本薬学会東北支部大会
  • Place of Presentation: いわき明星大学キャンパス，福島
  • Year and Date: 2014-10-05
• [Presentation] アントラニル酸含有環状ペプチドPF1171類の全合成と昆虫麻痺活性評価 (2014)
  • Author(s): 増田裕一，田中錬，甲斐建次，A. Ganesan，土井隆行
  • Organizer: 平成26年度化学系学協会東北大会
  • Place of Presentation: 山形大学米沢キャンパス，山形
  • Year and Date: 2014-09-20 – 2014-09-21
• [Presentation] 生物活性環状ペプチドの合成と三次元構造解析 (2014)
  • Author(s): 増田 裕一
  • Organizer: 第13回化学系若手研究者セミナー
  • Place of Presentation: 東北薬科大学70周年記念講堂，仙台
  • Year and Date: 2014-09-06
  • Invited
• [Presentation] Total Synthesis and Biological Evaluation of PF1171A, C, F, and G (2014)
  • Author(s): Yuichi Masuda, Ren Tanaka, Kenji Kai, A. Ganesan, and Takayuki Doi
  • Organizer: Tohoku University's Chemistry Summer School 2014
  • Place of Presentation: Tohoku University, Sendai，Miyagi
  • Year and Date: 2014-08-24 – 2014-08-27
• [Presentation] 固体NMRを用いた生体分子の分子間相互作用の解析 (2014)
  • Author(s): 増田 裕一
  • Organizer: 第49回天然物化学談話会 ショートトーク
  • Place of Presentation: せとうち児島ホテル，倉敷，岡山
  • Year and Date: 2014-07-02 – 2014-07-04
• [Remarks] 創薬化学研究室の紹介ページ
  • URL: http://www.cc.mie-u.ac.jp/~masuda/
• [Remarks] 三重大学教員紹介
  • URL: http://kyoin.mie-u.ac.jp/profile/3065.html
• [Remarks] 東北大学薬学部，大学院薬学研究科 反応制御化学分野のホームページ Doi Laboratory
  • URL: http://www.pharm.tohoku.ac.jp/~hannou/index.html
• [Remarks] 三重大学教員紹介
  • URL: http://www.bio.mie-u.ac.jp/academics/faculty/YuichiMasuda.html
• [Remarks] 東北大学薬学部 大学院薬学研究科 反応制御化学分野のホームページ
  • URL: http://www.pharm.tohoku.ac.jp/~hannou/index.html