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2022 Fiscal Year Final Research Report

Development of cationic peptides containing multiple alkyl chains as cell membrane permeation carriers for exogenous proteins

Research Project

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Project/Area Number 20K05705
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 37010:Bio-related chemistry
Research InstitutionNagoya Institute of Technology

Principal Investigator

Mizuno Toshihisa  名古屋工業大学, 工学(系)研究科(研究院), 准教授 (90345950)

Project Period (FY) 2020-04-01 – 2023-03-31
Keywordsペプチド界面活性剤 / 細胞膜透過キャリア
Outline of Final Research Achievements

We have developed and assessed a cell membrane permeation carrier, cpPG, which is based on a lipopeptide called PG-surfactant. This unique lipopeptide incorporates two alkyl chains within the side chains of the peptide backbone in a single molecule. In the initial stage, we evaluated the delivery efficiency of cpPG for high molecular weight exogenous proteins, using the tumor suppressor protein p53 (with a molecular weight of approximately 46 kDa), and confirmed its effective delivery. Furthermore, to achieve cell-type selective delivery, we designed a cell penetration carrier called cpPG-GE11. This carrier combines cpPG with the GE11 peptide moiety, which exhibits selective affinity for the epidermal growth factor receptor (EGFR). Consequently, by utilizing cpPG-GE11 as a cytosolic carrier, we successfully achieved preferential delivery of an inhibitory peptide against TGF-b; signaling to EGFR-overexpressing A431 cells.

Free Research Field

生体関連化学

Academic Significance and Societal Importance of the Research Achievements

新たなクラスのバイオ医薬品として、細胞内分子に直接作用可能な蛋白質の利用が考えられているが、これらは自発的には細胞内に浸透しないため、効率の良い細胞膜透過キャリア開発が、この課題解決のためのキーイシューとなっている。本研究ではアルキル鎖を側鎖に複数含む新たなクラスの細胞膜透過キャリアの開発を行い、その有効性を示すことに成功した。実際の利用のためには、より高い細胞種選択性や組織深部までの送達を可能とする技術開発もさらに必要とされるが、新たなクラスのリポペプチドが細胞膜透過キャリアとして有効性であることを明らかにできたことは、この分野の発展への貢献が十分に期待できる。

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Published: 2024-01-30  

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