Development of swich on-off type probes for detection of GPCR dimers

2013 Fiscal Year Final Research Report

• Project/Area Number: 24659043
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Drug development chemistry
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: TAMAMURA Hirokazu 東京医科歯科大学, 生体材料工学研究所, 教授 (80217182)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: GPCR / 二量体 / CXCR4 / がん細胞 / イメージング

Research Abstract

Assembly status of G protein-coupled receptors (GPCR) on the cellular surface is of great interest because the multimerization of GPCR could play pivotal roles in cellular functions. The bivalent ligands with polyproline linkers for CXCR4 have been shown to work as molecular ruler because of the rigid structure of polyproline helices. To expand the utility of the ligands with rigid linkers and explore the possible multimeric form of GPCR, the effect of near infrared dye labeling for the poly-L-proline linkers were addressed utilizing our bivalent-type CXCR4 ligand. The poly-L-proline linkers containing the NIR-dye at the middle or end of the linkers were prepared and their fluorescent and binding properties were analyzed to produce novel detection methods with a switch-on-off type .

Research Products

• [Journal Article] A CD4 Mimic as an HIV Entry Inhibitor : Pharmacokinetics (2013)
  • Author(s): Chie Hashimoto, Tetsuo Narumi, Hiroyuki Otsuki, Yuki Hirota, Hiroshi Arai, Kazuhisa Yoshimura, Shigeyoshi Harada, Nami Ohashi, Wataru Nomura, Tomoyuki Miura, Tatsuhiko Igarashi, Shuzo Matsushita & Hirokazu Tamamura
  • Journal Title: Bioorg. Med. Chem. Volume: 21(24) Pages: 7884–7889
• [Journal Article] CXCR4-derived Synthetic Peptides Inducing Anti-HIV-1 Antibodies (2013)
  • Author(s): Chie Hashimoto, Wataru Nomura, Tetsuo Narumi, Masayuki Fujino, Toru Nakahara, Naoki Yamamoto, Tsutomu Murakami & Hirokazu Tamamura
  • Journal Title: Bioorg. Med. Chem. Volume: 21(22) Pages: 6878–6885
• [Journal Article] Generation of a Replication-competent Simian–human Immunodeficiency Virus, the Neutralisation Sensitivity of Which can be Enhanced in the Presence of a Small Molecule CD4 Mimic (2013)
  • Author(s): Hiroyuki Otsuki, Takayuki Hishiki, Tomoyuki Miura, Chie Hashimoto, Tetsuo Narumi, Hir okazu Tamamur a, Kazuhisa Yoshimura, Shuzo Matsushita & Tatsuhiko Igarashi
  • Journal Title: J. Gen. Virol. Volume: 94(12) Pages: 2710–2716
• [Journal Article] Cell-Permeable Stapled Peptides Based on HIV-1 Integrase Inhibitors Derived from HIV-1 Gene Product (2013)
  • Author(s): Wataru Nomura, Haruo Aikawa, Nami Ohashi, Emiko Urano, Mathieu Metifiot, Masayuki Fujino, Kasthuraiah Maddali, Taro Ozaki, Ami Nozue, Tetsuo Narumi, Chie Hashimoto, Tomohiro Tanaka, Yves Pommier, Naoki Yamamoto, Jun Komano, Tsutomu Murakami & Hirokazu Tamamura
  • Journal Title: ACS Chem. Biol. Volume: 8(10) Pages: 2235–2244
• [Journal Article] Anti-HIV-1 Peptide Derivatives Based on the HIV-1 Co-receptor CXCR4 (2013)
  • Author(s): Chie Hashimoto, Wataru Nomura, Tetsuo Narumi, Masayuki Fujino, Hiroshi Tsutsumi, Masaki Haseyama, Naoki Yamamoto, Tsutomu Murakami & Hirokazu Tamamura
  • Journal Title: ChemMedChem Volume: 8(10) Pages: 1668-1672
• [Journal Article] Multimerized CHR-derived Peptides as HIV-1 Fusion Inhibitors (2013)
  • Author(s): Wataru Nomura, Chie Hashimoto, Takaharu Suzuki, Nami Ohashi, Masayuki Fujino, Tsutomu Murakami, Naoki Yamamoto & Hirokazu Tamamura
  • Journal Title: Bioorg. Med. Chem. Volume: 21(15) Pages: 4452–4458
• [Journal Article] CD4 Mimics as HIV Entry Inhibitors : Lead Optimization Studies of the Aromatic Substituents (2013)
  • Author(s): Tetsuo Narumi, Hiroshi Arai, Kazuhisa Yoshimura, Shigeyoshi Harada, Yuki Hirota, Nami Ohashi, Chie Hashimoto, Wataru Nomura, Shuzo Matsushita & Hirokazu Tamamura
  • Journal Title: Bioorg. Med. Chem. Volume: 21(9) Pages: 2518–2526
• [Journal Article] Low Molecular Weight CXCR4 Ligands with Variable Spacers (2013)
  • Author(s): Tetsuo Narumi, Haruo Aikawa, Tomohiro Tanaka, Chie Hashimoto, Nami Ohashi, Wataru Nomura, Takuya Kobayakawa, Hikaru Takano, Yuki Hirota, Tsutomu Murakami, Naoki Yamamoto & Hirokazu Tamamura
  • Journal Title: ChemMedChem Volume: 8(1) Pages: 118-124
• [Journal Article] Stereoselective Formation of Trisubstituted (Z)-Chloroalkenes Adjacent to a Tertiary Carbon Stereogenic Center by Organocuprate-Mediated Reduction/Alkylation (2012)
  • Author(s): Tetsuo Narumi, Takuya Kobayakawa, Haruo Aikawa, Shunsuke Seike & Hirokazu Tamamura
  • Journal Title: Org. Lett. Volume: 14(17) Pages: 4490-4493
• [Journal Article] Pharmacophore-based Small Molecule CXCR4 Ligands (2012)
  • Author(s): Tetsuo Narumi, Tomohiro Tanaka, Chie Hashimoto, Wataru Nomura, Haruo Aikawa, Akira Sohma, Kyoko Itotani, Miyako Kawamata, Tsutomu Murakami, Naoki Yamamoto & Hirokazu Tamamura
  • Journal Title: Bioorg. Med. Chem. Lett. Volume: 22(12) Pages: 4169-4172
• [Journal Article] Evaluation of a Synthetic C34 Trimer of HIV-1 gp41 as AIDS Vaccines (2012)
  • Author(s): Chie Hashimoto, Wataru Nomura, Aki Ohya, Emiko Urano, Kosuke Miyauchi, Tetsuo Narumi, Haruo Aikawa, Jun A. Komano, Naoki Yamamoto & Hirokazu Tamamura
  • Journal Title: Bioorg. Med. Chem. Volume: 20(10) Pages: 3287–3291