Development of early diagnostic methods for cancer tissue and metastasis utilizing bivalent GPCR ligands
Project/Area Number |
24390024
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Partial Multi-year Fund |
Section | 一般 |
Research Field |
Drug development chemistry
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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)
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Co-Investigator(Kenkyū-buntansha) |
NOMURA Wataru 東京医科歯科大学, 生体材料工学研究所, 准教授 (80463909)
NARUMI Testuo 東京医科歯科大学, 生体材料工学研究所, 助教 (50547867)
AIKAWA Haruo 東京医科歯科大学, 生体材料工学研究所, 特任助教 (70547322)
|
Project Period (FY) |
2012-04-01 – 2015-03-31
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Project Status |
Completed (Fiscal Year 2014)
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Budget Amount *help |
¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000)
Fiscal Year 2014: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2013: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
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Keywords | 分子標的 / GPCR / 分子プローブ / 創薬ツール / ケモカインレセプターCXCR4 / 2価結合型リガンド / 認識ユニット / がん / 2価結合型リガンド |
Outline of Final Research Achievements |
The assembly status of G protein-coupled receptors (GPCR) on the cellular surface is of interest because the multimerization of GPCR could play pivotal roles in cellular functions. A bivalent ligand with polyproline linkers for CXCR4 has been shown to serve as “molecular ruler” as a result of the rigid structure of polyproline helices. To expand the utility of the ligands with rigid linkers and explore the possible multimeric forms of GPCR, ligands with polyproline helices were newly designed and synthesized. The binding affinities of ligands for CXCR4 suggested that the ligands recognize the dimeric form of CXCR4 on the cellular surface. The fluorescent imaging and analysis by flow cytometry revealed that the ligand with 9-proline linkers binds to CXCR4 with remarkable specificity. The results of the present study suggest that the ligand design with rigid linkers is useful in the multimeric form.
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Report
(4 results)
Research Products
(12 results)
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[Journal Article] Development of a Fluoride-responsive Amide Bond Cleavage Device that is Potentially Applicable to a Traceable Linker.2014
Author(s)
5.Jun Yamamoto, Nami Maeda, Chiaki Komiya, Tomohiro Tanaka, Masaya Denda, Koji Ebisuno, Wataru Nomura, Hirokazu Tamamura, Youichi Sato, Aiko Yamauchi, Akira Shigenaga & Akira Otaka
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Journal Title
Tetrahedron,
Volume: 70-34
Pages: 5122-5127
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Cell-Permeable Stapled Peptides Based on HIV-1 Integrase Inhibitors Derived from HIV-1 Gene Products.2013
Author(s)
Nomura W, Aikawa H, Ohashi N, Urano E, Metifiot M, Fujino M, Maddali K, Ozaki T, Nozue A, Narumi T, Hashimoto C, Tanaka T, Pommier Y, Yamamoto N, Komano JA, Murakami T, Tamamura H.
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Journal Title
ACS Chem. Biol.
Volume: 8
Issue: 10
Pages: 2235-2244
DOI
Related Report
Peer Reviewed
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[Journal Article] Low Molecular Weight CXCR4 Ligands with Variable Spacers.2013
Author(s)
Narumi, T., Aikawa, H., Tanaka, T., Hashimoto、C., Ohashi, N., Nomura, W., Kobayakawa, T., Takano, H., Hirota, Y., Murakami, T., Yamamoto, N. and Tamamura, H.
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Journal Title
ChemMedChem
Volume: 8
Issue: 1
Pages: 118-124
DOI
Related Report
Peer Reviewed
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[Journal Article] Pharmacophore-Based Small Molecule CXCR4 Ligands.2012
Author(s)
Narumi, T., Tanaka, T., Hashimoto, C., Nomura, W., Aikawa, H., Sohma, A., Itotani, K., Kawamata, K., Murakami, T., Yamamoto, N. and Tamamura, H.
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Journal Title
Bioorg.Med. Chem. Lett.
Volume: 22
Issue: 12
Pages: 4169-4172
DOI
Related Report
Peer Reviewed
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