2001 Fiscal Year Final Research Report Summary
Molecular design of functional domain-mimics of receptors and ligands
| Project/Area Number |
11490029
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
広領域
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| Research Institution | Kagoshima University |
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Principal Investigator |
SUGIMURA Kazuhisa Kagoshima University, Faculty of Engineering, Professor, 工学部, 教授 (80127240)
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| Co-Investigator(Kenkyū-buntansha) |
HASHIGUCHI Shuhei Kagoshima University, Faculty of Engineering, Research Associate, 工学部, 助手 (40295275)
BABA Masanori Kagoshima University, Faculty of Medicine, Professor, 医学部, 教授 (70181039)
ITO Yuji Kagoshima University, Faculty of Engineering, Associate Professor, 工学部, 助教授 (60223195)
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| Project Period (FY) |
1999 – 2001
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| Keywords | Phage library / Peptide mimic / scFv / Human antibody / MCP-1 / IL-6 / Inhibitor / Molecular design |
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| Research Abstract |
We tested the approach to design the peptide mimics of the receptor/ligand-binding domain by panning a phage display library using their conformational epitope-recognizing monoclonal antibodies. We demonstrated the feasibility of this approach by the reports of Nature biotechnology (16 : 267-270, 1998) and J. Immunol. (161 : 6622-6628).
In this study, we attempted to design the mimic molecule of MCP-1 (monocyte chemoattractant protein-1) and IL-6. In the case of MCP-1, we successfully identified the MCP-1 peptide mimic motifs of 19 amino acids, named G25 and C27. Both motifs contain two cysteins in their sequences. The synthetic and intramolecularly disulfide-linked peptides of these motifs inhibited the chemotaxis induced by MCP-1, while their derivatives with serine in place of cysteine did not.
In the case of IL-6, we identified the #37 motif which specifically bound to human IL-6. The synthetic 13 amino acid peptide of #37 motif inhibited the proliferation of human KT-3 cell lines induced with the stimulation of IL-6. On the other hand, The #37 peptide showed no inhibition on the proliferation of murine MH60 which is the IL-6-dependent cell line.
Thus, the G25, C27 and #37 peptide may be the leading peptides with antagonistic activities and useful for the therapy of inflammatory and autoimmune diseases such as rheumatoid arthritis.
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[Publications] M. Kawamura, T. Naito, M. Ueno, T. Akagi, K. Hiraishi, I. Takai, M. Makino, T. Serizawa, K. Sugimura, M. Akashi, M. Baba: "Induction of mucosal IgA following intravaginal administration of inactivated HIV-1-capturing nanospheres in mice"J. Med. Virol.. 66. 291-298 (2002)
Description
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