2021 Fiscal Year Final Research Report
The development of new antibody drug discovery design by means of the bond replacement system based on the structure information
| Project/Area Number |
20K21676
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 57:Oral science and related fields
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| Research Institution | Osaka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
鈴木 守 大阪大学, 蛋白質研究所, 准教授 (40280507)
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| Project Period (FY) |
2020-07-30 – 2022-03-31
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| Keywords | 結合置換法 / 立体構造 / 情報 / 創薬 / 抗体医薬品 / 分子 / 分子標的薬 |
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| Outline of Final Research Achievements |
In this research, we attempted to generate the new antibody drug modeled on Cetuximab which was used for treatment of oral cancer. Concretely, based on the structural information of protein, the iso-peptide bond was replaced the disulfide bond which was an obstacle to expression the recombinant of antibody with Escherichia coli.The structure information was suggested that to form the iso-peptide bond was of importance as the following three point; the distance of main chain was about 7.7 A catalytic residue was acidic amino acids and environmental construction was Hydrophobic amino acids like Phenylalanine. The recombinant protein designed to the feature of iso-peptide was possible to expression in Escherichia coli, the other side, most of them was insoluble minutes. From now on, we will attempt to sophisticate the quality of the recombinant.
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| Free Research Field |
結晶構造解析
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、構造学的な分子内のIso-peptide結合形成における必要な条件を明らかにする事で、抗体医薬品内で、精製難易度を上げているジスルフィド結合を、より単純な発現でも作製可能なIso-peptide結合に置換する部位の候補の提示が可能になり、従来の作製法よりも安価にかつ大量に薬剤を精製する可能性を検討する事で、口腔がん治療において、より安価に薬物療法を受けることができる可能性を示した。さらに、現在、行っているリコンビナントタンパク質の精製品質の向上を行う事で、将来的な臨床応用の可能性を示した。
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