Development of pradimicin-based research tools in glycobiology

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K05712
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 37020:Chemistry and chemical methodology of biomolecules-related
• Research Institution: Nagoya University
• Principal Investigator: Nakagawa Yu 名古屋大学, 生命農学研究科, 准教授 (90452284)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: Pradimicin / 糖鎖 / 天然物 / マンノース / 糖タンパク質 / 研究用ツール

Outline of Final Research Achievements

Pradimicin A (PRM-A) is a unique natural product that binds D-mannose (Man). Although PRM-A holds great promise as research tools in glycobiology, the practical application of PRM-A has been severely limited by its inherent tendency to form water-insoluble aggregates. In this study, we found that structural modification at the C18 carboxy group or the disaccharide moiety of PRM-A effectively suppresses its aggregate-forming propensity. Based on this finding, we showed that structurally-modified derivatives of PRM-A can stain glycoproteins and fungi having Man-containing glycans. We also developed a semi-synthetic derivative of PRM-A, which can be connected to various functional molecules and thus would serve as a versatile compound for the future development of research tools in glycobiology.

Free Research Field

天然物化学

Academic Significance and Societal Importance of the Research Achievements

近年，生命現象の包括的理解には糖鎖の機能解明が不可欠であるとの認識が広まっており，ゲノミクス，プロテオミクスに並んでグライコミクスの重要性が急速に高まっている。グライコミクス研究においては“高分子”の糖結合性タンパク質が広く利用されているが，本研究では天然由来の糖結合性“低分子”も利用できることを初めて実証した。本研究で得られた成果は，糖鎖科学分野における天然物利用の新たな可能性を提示するものであり，糖鎖科学および天然物化学の両分野における学術的意義は大きいと考えられる。