Design of amphiphilic oligopeptides that induce destructive self-assembly of pathogenic amyloids

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K14471
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 27040:Biofunction and bioprocess engineering-related
• Research Institution: Kobe University
• Principal Investigator: Morita Kenta 神戸大学, 工学研究科, 助教 (60804127)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ペプチド / アルツハイマー病 / 自己組織化 / 鏡像異性体 / アミロイド

Outline of Final Research Achievements

In this study, we successfully designed a peptide that binds to amyloid-beta (Aβ), a key factor in Alzheimer's disease (AD), by utilizing the interactions between peptide enantiomers. Specifically, the amphiphilic peptide f5r6 was developed to disrupt the self-organization of Aβ, altering its aggregation from nanofibers to amorphous clumps. This breakthrough allowed for the rational design of peptides without the need for extensive screening traditionally required, opening new avenues for therapeutic development. The results not only challenge the previously held belief that peptide isomers do not interact but also demonstrate potential practical applications in drug development. This study provides significant academic insights into peptide functionalities and highlights their application in creating new treatment modalities for diseases. The approach promises to streamline the design of enzyme inhibitors and could revolutionize platforms for developing new therapeutic agents.

Free Research Field

バイオナノマテリアル

Academic Significance and Societal Importance of the Research Achievements

本研究では、ペプチドの鏡像異性体の相互作用を用いてADの原因因子Aβに結合するペプチドを設計した。設計された両親媒性ペプチドf5r6は、Aβの凝集形態を変化させ、「破壊的自己組織化」を実現した。これにより、従来必要であった大規模スクリーニングなしにペプチドを合理的に設計できるようになった。本成果は、これまでペプチドの鏡像異性体同士は相互作用を持たないと考えられていた常識を覆した点で学術的に意義深く、さらにそれが創薬などの実際的なアプリケーションに応用可能であることを示した点で社会的にも意義深い。