2020 Fiscal Year Final Research Report
Precise Synthetic Modifications of Proteins
Project/Area Number |
17H01522
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Research Category |
Grant-in-Aid for Scientific Research (A)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Chemical pharmacy
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Research Institution | The University of Tokyo |
Principal Investigator |
Kanai Motomu 東京大学, 大学院薬学系研究科(薬学部), 教授 (20243264)
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Project Period (FY) |
2017-04-01 – 2021-03-31
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Keywords | 抗体ー薬物複合体 / トリプトファン / 抗がん剤 / ラジカル / 官能基許容性 |
Outline of Final Research Achievements |
The goal of this project was to synthesize highly homogeneous antibody-drug conjugates (ADC) using the originally developed tryptophan-selective protein modification reaction and evaluate their activities. We synthesized keto-ABNO covalently bound to an anticancer drug. The molecules were conjugated to an antibody to produce ADCs with a controlled drug / antibody ratio. Those tryptophan-ADCs were toxic to cancer cells expressing antigens that bind to the antibody. It was shown that the tryptophan-ADCs can be synthesized with high homogeneity and has high potential as a novel anticancer agent.
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Free Research Field |
有機合成化学
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Academic Significance and Societal Importance of the Research Achievements |
副作用が低く、効果が高い抗がん剤の開発が広く望まれている。強い細胞毒性を持つ分子を抗体に結合させて、毒をがん細胞選択的に送り込む抗体ー薬物複合体は、そのような抗がん剤であると注目されている。従来の合成法では、抗体の様々な位置に不均質の結合数で薬物が結合した抗体ー薬物複合体しか作れなかった。一方で、我々が開発した方法を用いると、特定の位置に数を定めて抗体ー薬物複合体を合成できるようになった。この新しい抗体ー薬物複合体は、抗がん効果を示すことを明らかとした。
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