| Project/Area Number |
25242068
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biomolecular chemistry
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| Research Institution | Osaka Prefecture University |
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Principal Investigator |
Fujii Ikuo 大阪府立大学, 理学(系)研究科(研究院), 教授 (70189984)
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| Co-Investigator(Kenkyū-buntansha) |
TSUMURAYA Takeshi 大阪府立大学, 大学院理学系研究科, 准教授 (00372855)
藤原 大佑 大阪府立大学, 理学(系)研究科(研究院), 助教 (30611420)
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| Co-Investigator(Renkei-kenkyūsha) |
FUJIWARA Daisuke 大阪府立大学, 大学院理学系研究科, 助教 (30611420)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥47,320,000 (Direct Cost: ¥36,400,000、Indirect Cost: ¥10,920,000)
Fiscal Year 2015: ¥13,650,000 (Direct Cost: ¥10,500,000、Indirect Cost: ¥3,150,000)
Fiscal Year 2014: ¥13,650,000 (Direct Cost: ¥10,500,000、Indirect Cost: ¥3,150,000)
Fiscal Year 2013: ¥20,020,000 (Direct Cost: ¥15,400,000、Indirect Cost: ¥4,620,000)
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| Keywords | 分子標的医薬品 / ペプチド / 進化分子工学 / ファージ表層提示法 / ヘリックス構造 / 生体分子 / 医療・福祉福祉 / ナノバイオ / 蛋白質 / 有機化学 |
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| Outline of Final Research Achievements |
Despite intense research into the design of small ligands that target protein-protein interaction, a novel methodology for the rational design of such ligands remains an elusive goal. To design such ligands, our group has examined the directed evolution in a phage-displayed library of helix-loop-helix peptides. Screening of the library against targeted proteins provided bioactive peptides, whose rigid structures showed the spatial orientation of the pharmacophores, thus facilitating structure-based design of peptidomimetics. We constructed a phage-displayed library of the peptides and screened the library against several targeted proteins. The obtained peptide showed a strong binding affinity (Kd of 4 nM) , and a long half-life (>2 weeks) in mouse sera. In addition, the peptides provide structural information of the pharmacophores to facilitate structure-based design of peptidomimetics. Finally, we succeeded to generate biphenyl compounds binding to the targeted proteins.
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