Development of partially fluorinated lipid/membrane protein complex designed based on Stratified Dipole-Arrays model

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06568
• 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: National Institute of Advanced Industrial Science and Technology
• Principal Investigator: Takagi Toshiyuki 国立研究開発法人産業技術総合研究所, 生命工学領域, 主任研究員 (10248065)
• Co-Investigator(Kenkyū-buntansha): 園山 正史 群馬大学, 大学院理工学府, 教授 (40242242)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: ペルフルオロアルキル基 / 人工脂質 / 膜タンパク質 / 再構成膜 / バクテリオロドプシン

Outline of Final Research Achievements

Sufficient long perfluoroalkyl chains are strongly hydrophobic and more rigid than hydrocarbon ones, leading to the formation of rigid assemblies, of which properties are not suitable for membrane protein reconstitution matrices. Partially fluorinated phospholipid-based membranes, however, are greatly expected promising materials for reconstitution of membrane proteins.
In this study, we presented synthesis of phospholipids (DMPC and DPPC) having perfluoroalkyl groups of different lengths and their membrane properties. Our proposed fluorinated phospholipids designed based on Stratified Dipole-Arrays (SDA) model are considered effective to provide the mechanically stable and fluid membranes, essential for the construction of membrane protein reconstitution matrices.

Free Research Field

有機フッ素化学

Academic Significance and Societal Importance of the Research Achievements

膜タンパク質を標的とした医薬品開発において、脂質・膜タンパク質複合体膜は、医薬品スクリーニングの現場に有望である。そこで、脂質・膜タンパク質複合体膜における膜タンパク質の機能を長期安定維持可能な人工脂質の開発として、フッ素導入した擬環状型脂質の開発を目指している。SDA理論に基づく含フッ素化界面活性剤設計は、人工血管材料の表面修飾剤やリポソームDDS材料や臨床診断細胞分散剤などの医療やバイオ分野領域における研究開発を加速すると期待される。