A novel methodology for generation of molecular-targeting drugs via directed evolution in combinatorial libraries of conformationally constrained peptides
| 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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Report
(4 results)
Research Products
(74 results)
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[Journal Article] Development of an ultrasensitive immunoassay using affinity maturated antibodies for the measurement of rodent insulin2015
Author(s)
Sunao Imai, Shoichi Naito, Tatsuya Takahashi, Akira Yamauchi, Etsuo Nakamura, Masaaki Sato, Yuuichi Mitsuda, Hiroyuki Takagi, Yoshito Numata, Ikuo Fujii, Shoji Yamane
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Journal Title
Analytical Biochemistry
Volume: 473
Pages: 72-79
DOI
Related Report
Peer Reviewed
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[Journal Article] Development of a novel immunoassay specific for mouse intact proinsulin2015
Author(s)
Sunao Imai, Tatsuya Takahashi, Shoichi Naito, Akira Yamauchi, Chihiro Okada, Yoshihide Notsu, Ikue Sakikawa, Michiyoshi Hatanaka, Takanori Iwasaki, Atsushi Morita, Ikuo Fujii, Shoji Yamane
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Journal Title
Analytical Biochemistry
Volume: 484
Pages: 91-98
DOI
Related Report
Peer Reviewed
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[Journal Article] The cyclized helix-loop-helix peptide as a molecular scaffold for the design of intracellular protein-protein interaction inhibitors2015
Author(s)
Daisuke Fujiwara, Hidekazu Kitada, Masahiro Oguri, Toshio Nishihara, Masataka Michigami, Kazunori Shiraishi, Eiji Yuba, Ikuhiko Nakase, Seiji Kodama, Kenji Kono, Sihyun Ham, Ikuo Fujii
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Journal Title
Peptide Science
Volume: 2015
Pages: 85-86
Related Report
Peer Reviewed
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[Journal Article] An automated system for high-throughput single cell-based breeding2013
Author(s)
Nobuo Yoshimoto, Akiko Kida, Xu Jie, Masaya Kurokawa, Masumi Iijima, Tomoaki Niimi, Andrés D. Maturana, Itoshi Nikaido, Hiroki R. Ueda, Kenji Tatematsu, Katsuyuki Tanizawa, Akihiko Kondo, Ikuo Fujii, Shun'ichi Kuroda
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Journal Title
Scientific Reports
Volume: 3
Issue: 1
Pages: 1191-1191
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] CYCLIZED HELIX-LOOP-HELIX PEPTIDE AS A MOLECULAR SCAFFOLD FOR THE DESIGN OF INTRACELLULAR PROTEIN-PROTEIN INTERACTION INHIBITORS2015
Author(s)
Daisuke Fujiwara, Hidekazu Kitada, Masahiro Oguri, Toshio Nishihara, Masataka Michigami, Kazunori Shiraishi, Eiji Yub, Ikuhiko Nakase, Seiji Kodama, Kenji Kono, Sihyun Ham, and Ikuo Fujii
Organizer
第52回ペプチド討論会
Place of Presentation
平塚市中央公民館, 神奈川県
Year and Date
2015-11-16
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