Organic chemistry-based approaches for biomolecules modification under multimolecular crowding biosystems

2022 Fiscal Year Final Research Report

• Project Area: Chemical Approaches for Miscellaneous / Crowding Live Systems
• Project/Area Number: 17H06348
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Science and Engineering
• Research Institution: Kyoto University
• Principal Investigator: Hamachi Itaru 京都大学, 工学研究科, 教授 (90202259)
• Project Period (FY): 2017-06-30 – 2022-03-31
• Keywords: 分子夾雑化学 / 生命化学 / ケミカルバイオロジー / リガンド指向性化学 / 超分子化学 / 生体関連化学

Outline of Final Research Achievements

In line with the initial research proposal aiming to explore the "Organic chemistry in multimolecular crowding conditions", we developed new organic chemical reactions that can work in live cells, and clarified their reaction characteristics (reaction kinetics, reaction selectivity for functional groups, and stability in crowding conditions). Specifically, we conducted (1) development of novel ligand-directed chemistry and its application to chemical labeling of receptor proteins and design of covalent inhibitors for disease-associated proteins, (2) development of novel reaction systems that allow the specific labeling of biomolecules (lipids and proteins) in particular environments or organelles in live cells and application of this techniques to the imaging analysis of intracellular dynamics of biomolecules under live cell conditions. (3) design and biomimetic construction of artificial molecular crowding systems by employing the supramolecular multi-component composite systems.

Free Research Field

ケミカルバイオロジー

Academic Significance and Societal Importance of the Research Achievements

細胞や組織内のような夾雑系における生体分子の振る舞いは、分子夾雑系で機能する分子ツールの整備が不十分であったために、その分子論的理解は遅々として進んでいないのが現状であった。本研究で得られた成果は、細胞や生きた動物体内など分子夾雑環境下における実際のタンパク質や脂質など生体分子の挙動や機能を系統的かつ定量的に解明することを目指す「分子夾雑の化学」という新しい学問分野の創造に、有機化学的な側面から貢献することが期待される。また、本研究で開発した分子夾雑環境で機能する有機化学的手法や人工分子のデザイン法は、新たな薬剤、診断技術の開発や次世代マテリアルや再生医療材料の開発に向けた貢献が期待できる。