Design and synthesis of molecular probes useful for the development of molecular-targeted chemotherapeutics for triple-negative breast cancer

• Project/Area Number: 22790005
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Chemical pharmacy
• Research Institution: Gunma University
• Principal Investigator: YAMADA Keiichi 群馬大学, 大学院・工学研究科, 助教 (70323334)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: トリプルネガティブ乳癌 / 環状ペプチド / 分子プローブ / 標識合成 / 薬物動態

Research Abstract

SA-X is a N-methylated cyclic peptide containing Phe(4-X)(X=Br, I) residue exhibiting potent antitumor activity against triple-negative breast cancer (TNBC). In this study, we designed and synthesized molecular probes useful for the development of molecular targeted chemotherapeutics for TNBC.(1) SA-I was successfully conjugated with biotin-or fluorophore-tagged polyproline rod.(2) Radioiodine-labeled SA-I (SA-[^<125>I]) was synthesized via tin-radioiodine exchange reaction. SA-[^<125>I] showed high accumulation in liver and intestine after administration to in normal and tumor-bearing mice. In addition, SA-[^<125>I] hardly accumulated in tumor.

Research Products

• [Journal Article] Efficient solid-phase synthesis of cyclic RGD peptides under controlled microwave heating (2012)
  • Author(s): K. Yamada, I. Nagashim M. Hachisu, I. Matsuo, H. Shimizu
  • Journal Title: Tetrahedron Lett Volume: 53 Pages: 1066-1070
  • Peer Reviewed
• [Journal Article] Efficient solid-phase synthesis of cyclic RGD peptides under controlled microwave heating (2012)
  • Author(s): K.Yamada, et al.
  • Journal Title: Tetrahedron Letters Volume: 53 Issue: 9 Pages: 1066-1070
  • DOI: 10.1016/j.tetlet.2011.12.069
  • Peer Reviewed
• [Journal Article] Synthesis and in vivo evaluation of radiohalogen-labeled antitumor cyclicpeptides (2012)
  • Author(s): K.Yamada, et al.
  • Journal Title: Peptide Science 2011 Pages: 287-290
  • NAID: 10030204416
  • Peer Reviewed
• [Journal Article] Synthesis and in vivo evaluation of radiohalogen-labeled antitumor cyclic peptides (2011)
  • Author(s): K. Yamada, S. Watanabe, Y, Ohshima, H. Hanaoka, N. Tsukui, C. Takano, A. Yamaguchi, H. Oku and N. S. Ishioka
  • Journal Title: Peptid Science 211 Pages: 287-290
  • NAID: 10030204416
  • Peer Reviewed
• [Journal Article] Structure-activity relationships of gramicidin S analogs containing (β-3-pyridyl)-α,β-dehydroalanine residues on membrane permeability (2011)
  • Author(s): K. Yamada, M. Kodaira, S. Shinoda, K. Komagoe, H. Oku, R. Katakai, T. Katsu, I. Matsuo
  • Journal Title: Med. Chem. Commun Volume: 2 Pages: 644-649
  • Peer Reviewed
• [Journal Article] Structure-activity relationships of gramicidin S analogs containing (ss-3-pyridyl)-α,β-dehydroalanine residues on membrane permeability (2011)
  • Author(s): Keiichi Yamada, et al.
  • Journal Title: Medicinal Chemistry Communications Volume: 2(印刷中)
  • Peer Reviewed
• [Journal Article] Syntheses of fluorescent peptides labeled with 7-diethylaminocoumarin and their photophysical properties in liposome membranes. (2011)
  • Author(s): Tokiko Murase, et al.
  • Journal Title: Peptide Science 2010 Volume: (印刷中)
  • Peer Reviewed
• [Presentation] 生物活性ペプチドの標識合成に関する基礎的検討 (2011)
  • Author(s): 山田景子, 山田圭一, 渡邊茂樹, 奥浩之, 石岡典子
  • Organizer: 日本化学会関東支部群馬地区地域懇談会
  • Place of Presentation: 群馬
  • Year and Date: 2011-12-10
• [Presentation] ^125I標識環状ペプチドSansalvamide A誘導体の合成と評価 (2011)
  • Author(s): 渡邊茂樹, 山田圭一, 大島康宏, 花岡宏史, 津久井匠隆, 高野智香子, 山口藍子, 奥浩之, 飯田靖彦, 遠藤啓吾, 石岡典子
  • Organizer: 第11回放射性医薬品・画像診断薬研究会
  • Place of Presentation: 京都
  • Year and Date: 2011-12-03
• [Presentation] ^<125>I標識環状ペプチドSansalvamide A誘導体の合成と評価 (2011)
  • Author(s): 渡邊茂樹、山田圭一、大島康宏、花岡宏史、津久井匠隆、高野智香子、山口藍子、奥浩之、飯田靖彦、遠藤啓吾、石岡典子
  • Organizer: 第11回放射性医薬品・画像診断薬研究会
  • Place of Presentation: 京都
  • Year and Date: 2011-12-03
• [Presentation] The revival of cationic peptide antibiotics : Design and synthesis of membrane-active cyclic peptides based on gramicidin S and polymyxin B (2011)
  • Author(s): Keiichi Yamada
  • Organizer: 5th China Medical Biotech Forum
  • Place of Presentation: Beijing, China
  • Year and Date: 2011-11-09
• [Presentation] The rivival of cationic peptide antibiotics : Design and synthesis of membrane-active cyclic peptides based on gramicidin S and polymyxin B (2011)
  • Author(s): K. Yamada
  • Organizer: 5th China Medical Biotech Forum
  • Place of Presentation: Beijing, China
• [Presentation] 放射性ハロゲンで標識化した抗腫瘍活性ペプチドの合成とin vivo動態評価 (2011)
  • Author(s): 山田圭一, 渡辺茂樹, 大島康宏, 花岡宏史, 津久井匠隆, 高野智香子, 山口藍子, 奥浩之, 石岡典子
  • Organizer: 第48回ペプチド討論会
  • Place of Presentation: 札幌
• [Presentation] N-メチル化ペプチドの合成におけるマイクロ波効果 (2011)
  • Author(s): 中島徹也, 山田圭一, 長島生, 奥浩之, 松尾一郎, 清水弘樹
  • Organizer: 日本化学会第91春季年会
  • Place of Presentation: 神奈川
• [Presentation] Microwave-assisted solid-phase synthesis of hindered N-methyl peptides (2010)
  • Author(s): Keiichi Yamada, et al.
  • Organizer: The International Chemical Congress of Pacific Basin Societies
  • Place of Presentation: Honolulu, Hawaii, USA
  • Year and Date: 2010-12-18
• [Presentation] Solid-phase synthesis of cyclic peptides containing p-(tri-n-butyl-stannyl)-phenylalanine residue (2010)
  • Author(s): Narutaka Tsukui, et al.
  • Organizer: The International Chemical Congress of Pacific Basin Societies
  • Place of Presentation: Honolulu, Hawaii, USA
  • Year and Date: 2010-12-18
• [Presentation] 生理活性ペプチドのイメージングを目指した芳香族アミノ酸の標識合成 (2010)
  • Author(s): 津久井匠隆, 渡辺茂樹, 花岡宏史, 山田圭一, 奥浩之, 松尾一郎, 遠藤啓吾, 石岡典子
  • Organizer: 第47回アイソトープ・放射線研究会
  • Place of Presentation: 東京
  • Year and Date: 2010-07-07
• [Presentation] Solid-phase synthesis of cyclic peptides containing p-[tri-(n-butyl)-stannyl]phenylalanine residue (2010)
  • Author(s): N. Tsukui, K. Yamada, S. Watanabe, H. Hanaoka, H. Oku, K. Endo, N. S. Ishioka, I. Matsuo
  • Organizer: PacifiChem 2010
  • Place of Presentation: Hawaii, USA
• [Presentation] Microwave-assisted Solid-phase Synthesis of hindered N-methyl peptides (2010)
  • Author(s): K. Yamada, I. Nagashima, M. Hachisu, H. Oku, H. Shimizu, I. Matsuo
  • Organizer: PacifiChem 2010
  • Place of Presentation: Hawaii, USA
• [Presentation] Syntheses of fluorescent peptides labeled with 7-diethylaminocoumarin and their photophysical properties in liposome membranes (2010)
  • Author(s): T. Murase, T. Yoshihara, K. Yamada, S. Tobita
  • Organizer: 5th International Peptide Symposium
  • Place of Presentation: Kyoto
• [Presentation] がんのPETイメージング薬剤としての^<76>Br標識アミノ酸の有用性 (2010)
  • Author(s): 花岡宏史, 渡辺茂樹, 富永英之, 大島康宏, 津久井匠隆, 渡辺智, 山田圭一, 飯田靖彦, 織内昇, 樋口徹也, 石岡典子, 遠藤啓吾
  • Organizer: 第5回日本分子イメージング学会学術総会
  • Place of Presentation: 滋賀
• [Remarks]
  • URL: http://www.chem-bio.gunma-u.ac.jp/~peptidechem/index.html