2009 Fiscal Year Final Research Report
Development of Novel Screening Systems for Receptor Ligands
| Project/Area Number |
20790098
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Drug development chemistry
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| Research Institution | Kyoto University |
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Principal Investigator |
OISHI Shinya Kyoto University, 薬学研究科, 講師 (80381739)
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| Project Period (FY) |
2008 – 2009
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| Keywords | CXCR4 / スクリーニング / ケモカイン / HIV / 構造活性相関 |
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| Research Abstract |
Novel bioassay systems have been established for ligand screening to chemokine receptor CXCR4. Using a fluorescent CXCR4 antagonist probe, the receptor binding of potential CXCR4 ligands was quantitatively evaluated by flow cytometry. This facile approach would be applicable to the other receptors of peptide hormones and cytokines. The fluorescent SDF-1 derivatives have also been developed as novel agonist-based probes, which successfully detected the receptor internalization process of CXCR4. Furthermore, in order to investigate the bioactive conformations of CXCR4 antagonist, FC131, the structure-activity relationship study was performed using a series of alkene-type dipeptide isostere. It was demonstrated that both Tyr carbonyl oxygen and Arg N-alkyl group would predominantly contribute to the local conformations of FC131.
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[Journal Article] Synthesis and biological evaluation of selective CXCR4 antagonists containing alkene dipeptide isosteres.2010
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(3)
Pages: 616-621
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[Journal Article] Bioorganic synthesis of a recombinant HIV-1 fusion inhibitor, SC35EK, with an N-terminal pyroglutamate capping group from recombinant protein.2009
Author(s)
Kajiwara K., Watanabe K., Tokiwa R., Kurose T., Ohno H., Tsutsumi H., Hata Y., Izumi K., Kodama E., Matsuoka M., Oishi S., Fujii N.
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Journal Title
Bioorg.Med.Chem. 17(23)
Pages: 7964-7970
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[Journal Article] Bioorganic synthesis of end-capped anti-HIV peptides by simultaneous cyano-cysteine-mediated cleavages of recombinant proteins.2009
Author(s)
Tanaka M., Kajiwara K., Tokiwa R., Watanabe K., Ohno H., Tsutsumi H., Hata Y., Izumi K., Kodama E., Matsuoka M., Oishi S., Fujii N.
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Journal Title
Bioorg.Med.Chem. 17(21)
Pages: 7487-7492
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[Journal Article] Design and synthesis of membrane fusion inhibitors against the feline immunodeficiency virus.2009
Author(s)
Oishi S., Kodera Y., Nishikawa H., Kamitani H., Watabe T., Ohno H., Tochikura T., Shimane K., Kodama E., Matsuoka M., Mizukoshi F., Tsujimoto H., Fujii N.
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Journal Title
Bioorg.Med.Chem. 17(14)
Pages: 4916-4920
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[Journal Article] Peptide bond mimicry by (E)-alkene and (Z)-fluoroalkene peptide isosteres : synthesis and bioevaluation of alpha-helical anti-HIV peptide analogues.2009
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. 7(14)
Pages: 2872-2877
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[Journal Article] dentification of novel nonpeptide CXCR4 antagonists by ligand-based design approach.2008
Author(s)
Ueda S., Kato M., Inuki S., Ohno H., Evans B., Wang Z., Peiper S.C., Izumi K., Kodama E., Matsuoka M., Nagasawa H., Oishi S., Fujii N.
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Journal Title
Bioorg.Med.Chem.Lett. 18(14)
Pages: 4124-4129
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