Construction of a Peptide Drug Discovery Platform Using Chemically Modified Peptide Phage Libraries

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H02838
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 37020:Chemistry and chemical methodology of biomolecules-related
• Research Institution: Tokyo Institute of Technology
• Principal Investigator: Mihara Hisakazu 東京工業大学, 生命理工学院, 教授 (30183966)
• Co-Investigator(Kenkyū-buntansha): 堤 浩 東京工業大学, 生命理工学院, 准教授 (70398105) ; 三木 卓幸 東京工業大学, 生命理工学院, 助教 (20823991)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: ペプチド / ファージ提示 / 薬剤複合体 / タンパク質相互作用

Outline of Final Research Achievements

As the development of alternative molecules to antibody drugs, the discovery of small molecule-peptide conjugates using large libraries such as phage display methods has been attracting attention. In this study, we aimed to obtain small molecule-peptide conjugates that possess both the protein active center directivity of small molecules and the protein surface recognition properties of peptides by utilizing peptide phage libraries. Various peptide phage libraries modified with small molecules were successfully obtained by genetic engineering and synthetic chemistry. By screening against disease-related proteins, small molecule-peptide conjugates that bind to the target proteins were obtained.

Free Research Field

生物分子化学

Academic Significance and Societal Importance of the Research Achievements

本研究は、低分子修飾（化学的手法）とファージディスプレイ法（分子生物学的手法）を融合させて研究代表者等が独自に開発した標的指向型ファージディスプレイ法を駆使して、標的タンパク質に対して特異的なペプチド分子を創出するものであり、抗体医薬に続く新しい創薬モダリティとしてのペプチド創薬の発展に貢献するものとして、学術的および社会的意義の高い研究として位置づけられる。