Synthetic Studies on Amide Bond Isosteres and Their Application to Artificial CXCR4 Ligands
Project/Area Number |
21890113
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Research Category |
Grant-in-Aid for Research Activity Start-up
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Allocation Type | Single-year Grants |
Research Field |
Drug development chemistry
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Research Institution | Tokyo Medical and Dental University |
Principal Investigator |
NARUMI Tetsuo Tokyo Medical and Dental University, 生体材料工学研究所, 助教 (50547867)
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Project Period (FY) |
2009 – 2010
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Project Status |
Completed (Fiscal Year 2010)
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Budget Amount *help |
¥2,652,000 (Direct Cost: ¥2,040,000、Indirect Cost: ¥612,000)
Fiscal Year 2010: ¥1,261,000 (Direct Cost: ¥970,000、Indirect Cost: ¥291,000)
Fiscal Year 2009: ¥1,391,000 (Direct Cost: ¥1,070,000、Indirect Cost: ¥321,000)
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Keywords | 医薬品化学 / アミド結合等価体 / ジペプチドイソスター / クロロアルケン / シスアミド等価体 / α,α-ジクロロ-βt-アミノ酸 |
Research Abstract |
Replacement of the planar amide bond with a surrogate alkene substructure represents a promising approach to overcome their major limitations such as poor bioavailability and short physiological half-life, which limit their medicinal and biological use. However, development of effective ground state isosteric and isoelectronic analogues of the amide bond have yet to be developed. In this study, synthetic methodologies for a newly designed chloroalkene dipeptide isosteres (CADIs) were examined to develop diastereoselective, divergent, and practical synthetic approaches toward (Z)-chlororalkene and (E)-chloroalklene isostere skeletons utilizing organocopper-mediated reactions. These studies should contribute to the development of peptidomimetics-based medicinal chemistry.
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Report
(3 results)
Research Products
(97 results)
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[Journal Article] Azamacrocyclic-metal Complexes as CXCR4 Antagonists2011
Author(s)
T.Tanaka, T.Narumi, T.Ozaki, A.Sohma, N.Ohashi, C.Hashimoto, K.Itotani, W.Nomura, T.Murakami, N.Yamamoto, H.Tamamura, 他
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Journal Title
ChemMedChem 6巻
Pages: 834-839
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Peer Reviewed
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[Journal Article] CD4 mimics targeting the HIV entry mechanism and their hybrid molecules with a CXCR4 antagonist2010
Author(s)
T.Narumi, C.Ochiai, K.Yoshimura, S.Harada, T.Tanaka, W.Nomura, H.Arai, T.Ozaki, N.Ohashi, S.Matsushita, H.Tamamura, 他
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Journal Title
Bioorg.Med.Chem.Lett. 20巻
Pages: 5853-5858
Related Report
Peer Reviewed
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[Journal Article] Peptidic HIV integrase inhibitors derived from HIV gene products : structure-activity relationship studies2010
Author(s)
S.Suzuki, K.Maddali, C.Hashimoto, E.Urano, N.Ohashi, T.Tanaka, T.Ozaki, H.Arai, H.Tsutsumi, T.Narumi, W.Nomura, N.Yamamoto, Y.Pommier, JA Komano, H.Tamamura, 他
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Journal Title
Bioorg.Med.Chem. 18巻
Pages: 6771-6775
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Peer Reviewed
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[Journal Article] Peptide HIV-1 Integrase Inhibitors from HIV-1 Gene Products2010
Author(s)
S.Suzuki, E.Urano, C.Hashimoto, H.Tsutsumi, T.Nakahara, T.Tanaka, Y.Nakanishi, K.Maddali, Y.Han, M.Hamatake, K.Miyauchi, Y.Pommier, JA.Beutler, W.Sugiura, H.Fuji, T.Hoshino, K.Itotani, W.Nomura, T.Narumi, N.Yamamoto, JA.Komano, H.Tamamura, 他
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Journal Title
J.Med.Chem. 53巻
Pages: 5356-5360
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Peer Reviewed
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[Journal Article] Remodeling of dynamic structures of HIV-1 envelope proteins leads to synthetic antigen molecules including neutralizing antibodies2010
Author(s)
T.Nakahara, W.Nomura, K.Ohba, A.Ohya, T.Tanak, C.Hashimoto, T.Narumi, T.Murakami, N.Yamamoto, H.Tamamura, 他
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Journal Title
Bioconjugate Chem. 21巻
Pages: 709-714
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Peer Reviewed
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[Journal Article] Synthesis of Biological Evaluation of Selective CXCR4 Antagonists Containing Alkene Dipeptide Isosteres2010
Author(s)
Narumi T, Hayashi R, Tomita K, Kobayashi K, Tanahara N, Ohno H, Naito T, Kodama E, Matsuoka M, Oishi S, Fujii N.
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Journal Title
Org.Biomol.Chem. 8
Pages: 616-621
Related Report
Peer Reviewed
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[Journal Article] Synthesis and biological evaluation of selective CXCR4 antagonists containing alkene dipeptide isosteres2009
Author(s)
T.Narumi, R.Hayashi, K.Tomita, K.Kobayashi, N.Tanahara, H.Ohno, T.Naito, E.Kodama, M.Matsuoka, S.Oishi, N.Fujii, 他
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Journal Title
Org.Biomol.Chem.
Pages: 616-621
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Peer Reviewed
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[Journal Article] Structure-activity relationship study on artificial CXCR4 ligand possessing the cyclic pentapeptide scaffold : the exploration of amino acid residues of pentapeptides by substitutions of several aromatic amino acids2009
Author(s)
T.Tanaka, W.Nomura, T.Narumi, A.Esaka, S.Oishi, N.Ohashi, K.Itotani, B.J.Evans, Z.-X.Wang, S.C.Peiper, N.Fujii, H.Tamamura, 他
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Journal Title
Org.Biomol.Chem.
Pages: 3805-3809
Related Report
Peer Reviewed
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[Journal Article] Peptide Bond Mimicry by (E)-Alkene and (Z)-Fluoroalkene Peptide Isosteres : Synthesis and Bioevaluation of α-Helical Anti-HIV Peptide Analogues2009
Author(s)
S.Oishi, H.Kamitani, Y.Kodera, K.Watanabe, K.Kobayashi, T.Narumi, K.Tomita, H.Ohno, T.Naito, E.Kodama, M.Matsuoka, N.Fujii, 他
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Journal Title
Org.Biomol.Chem.
Pages: 2872-2877
Related Report
Peer Reviewed
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[Journal Article] Structure-activity relationship study on artificial CXCR4 ligands possessing the cyclic pentapeptide scaffold : the exploration of amino acid residues of pentapeptides by substitutions of several aromatic amino acids2009
Author(s)
Tanaka T, Nomura W, Narumi T, Esaka A, Oishi S, Ohashi N, Itotani K, Evans BJ, Wang Z, Peiper SC, Fujii N, Tamamura H.
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Journal Title
Org.Biomol.Chem. 7
Pages: 3805-3809
Related Report
Peer Reviewed
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[Journal Article] Peptide Bond Mimicry by(E)-Alkene and(Z)-Fluoroalkene Peptide Isosteres : Synthesis and Bioevaluation of α-Helical Anti-HIV Peptide Analogues2009
Author(s)
Oishi S, Kamitani H, Kodera Y, Watanabe K, Kobayashi K, Narumi T, Tomita K, Ohno H, Naito T, Kodama E, Matsuoka M, Fujii N.
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Journal Title
Org.Biomol.Chem. 14
Pages: 2872-2877
Related Report
Peer Reviewed
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[Presentation] Development of Small CD4 Mimic Molecules that Induce Conformational Changes in gp120.2010
Author(s)
Arai H, Narumi T, Ochiai C, Yoshimura K, Harada S, Tanaka T, Nomura W, Ozaki T, Ohashi N, Matsushita S, Tamamura H
Organizer
11th KUMAMOTO AIDS Seminer・GCOE Joint International Symposium.
Place of Presentation
Kumamoto, Japan
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[Presentation] Diastereoselective synthesis of (Z)-fluoroalkene dipeptide isosteres and their incorporation into the selective CXCR4 antagonists.2009
Author(s)
Narumi T, Hayashi R, Tomita K, Kobayashi K, Tanahara N, Ohno H, Naito T, Kodama E, Matsuoka M, Nomura W, Tamamura H, Oishi S, Fujii N.
Organizer
The 3rd Asia-Pacific International Peptide Symposium.
Place of Presentation
Jeju Island, Korea
Related Report
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[Presentation] Diastereoselcctive synthesis of (Z)-fluoroalkene dipeptide isosteres and their incorporation into the selective CXCR4 antagonists2009
Author(s)
Narumi T, Hayashi R, Tomita K, Kobayashi K, Tanahara N, Ohno H, Naito T, Kodama E, Matsuoka M, Nomura W, Tamamura H, Oishi S, Fujii N.
Organizer
The 3rd Asia-Pacific International Peptide Symposium
Place of Presentation
Jeju Island, Korea
Related Report
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[Presentation] キナーゼの細胞内局在機構解明のためのツールとしてのケージド化合物2009
Author(s)
野村渉, 芹澤雄樹, 大橋南美, Nancy E.Lewin, 奥田善章, 鳴海哲夫, 吉田清嗣, Peter M.Blumberg, 古田寿昭, 玉村啓和
Organizer
第24回生体機能関連化学シンポジウム,第12回バイオテクノロジー部会シンポジウム
Place of Presentation
福岡
Related Report
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[Presentation] ペプチドライブラリーを基にしたHIV-1インテグラーゼに対する阻害剤の創製2009
Author(s)
中西勇太, 中原徹, 鈴木慎太郎, 田中智博, 大橋南美, 堤浩, 鳴海哲夫, 野村渉, 駒野淳, 山本直樹, 玉村啓和
Organizer
第28回メディシナルケミストリーシンポジウム
Place of Presentation
東京
Related Report
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[Book] Peptide Science 20092010
Author(s)
Tanaka T, Nomura W, Narumi T, Yoshimura K, Matsushita S, Murakami T, Komano J, Yamamoto N, Tamamura H.
Total Pages
2
Publisher
Kouji Okamoto(Eds.), The Japanese peptide Society, Osaka
Related Report
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[Book] Peptide Science 20082009
Author(s)
Kobayashi K, Narumi T, Oishi S, Ohno H, Fujii N.
Total Pages
2
Publisher
Motoyoshi Nomizu(Eds.), The Japanese peptide Society, Osaka
Related Report
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