Design of Multi-FLAP as a high-performance antibody alternative protein

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K06970
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47010:Pharmaceutical chemistry and drug development sciences-related
• Research Institution: Tokyo Institute of Technology
• Principal Investigator: Kadonosono Tetsuya 東京工業大学, 生命理工学院, 助教 (10510282)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 中分子創薬 / 創薬デザイン技術 / タンパク質分子設計 / 抗体代替分子 / 標的結合小型タンパク質

Outline of Final Research Achievements

Antibody drugs have been extensively developed as molecular-targeted therapeutic drugs for various diseases including cancer. However, since an antibody has a large molecular size and a complex structure, its clinical application is limited. Therefore, a design strategy for developing the small antibody mimetics is required.
In this study, we successfully developed an antibody mimetic small protein, Multi-FLAP, which is one-fifteenth the size of an antibody, by computational design and screening. We also found that by designing two antigen-binding regions in one molecule, a strong binding affinity can be obtained due to the synergistic effect. Furthermore, we have developed a strategy to improve pharmacokinetics of Multi-FLAP for future clinical applications.

Free Research Field

創薬科学

Academic Significance and Societal Importance of the Research Achievements

抗体医薬は分子サイズが大きく複雑な構造を持つため、適用疾患が限られることや、製造コストおよび治療コストが非常に高額であることなど、新たな課題が顕在化している。本研究でデザイン理論を構築したMulti-FLAPは、分子サイズが小さいため化学合成で安価に調整でき、さらに組織浸透性の向上により適用疾患の拡大に繋がると期待できる。本研究はすべての人々に安価かつ高品質な医療を提供することを目指している。