2012 Fiscal Year Final Research Report
Microantibody: Directed evolution ofMolecular-targeting Peptides in Phage-displayed Libraries
| Project/Area Number |
23655161
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Chemistry related to living body
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| Research Institution | Osaka Prefecture University |
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Principal Investigator |
FUJII Ikuo 大阪府立大学, 大学院・理学系研究科, 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)
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| Project Period (FY) |
2011 – 2012
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| Keywords | ペプチド / 進化分子工学 / ファージライブラリー / 分子標的医薬 / 試験管内進化法 / 抗体 |
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| Research Abstract |
Use of antibody medicines has been limited due to the biophysical properties, immunogenicity, non-cell permeability, high cost to manufacture, and so on. To enable new applications where antibodies showsome limitations, we have developed an alternative-binding molecule with non-immunoglobulin domain. The molecule is a helix- loop- helix peptide. In previous work, we constructed a phage-displayed library of the helix-loop-helix peptides and then screened the library for G-CSF receptor to obtain a molecular-targeting peptide. Here, we examined the ability of the binding peptide as an alternative to antibody medicines. The peptide showed strong binding affinity (K_d: 4 nM) to the receptor, an enzyme-resistant property(half-life: 15 days in mouse sera), and non-immunogenicity. This peptide is named “microAntibodes” due to having the same properties as those of antibodies. Furthermore, we examined to screen the library of helix-loop-helix peptides against VEGF to successfully gain a tight-binding peptide. The semi-rational strategy, which combines directed evolution with de novodesign, provides a new way to generate a post-antibody therapy.
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[Journal Article] An automated system for high-throughput single cell-based breeding2013
Author(s)
Nobuo Yoshimoto,Akiko Kida, Masaya Kurokawa, Masumi Iijima, Tomoaki Nimi, Andres D. Maturana, Itoshi Nikaido, Hiroki R. Ueda, Kenji Tatematsu, Katsuyuki Tanizawa, Akihiko Kondo, Ikuo Fujii, Shun'ichi Kuroda
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Journal Title
Sci Rep
Volume: 3
Pages: 1-9
DOI
Peer Reviewed
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