Development of Medium-Molecular Glycomimetics

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K19053
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 37:Biomolecular chemistry and related fields
• Research Institution: Kyushu University
• Principal Investigator: Hirai Go 九州大学, 薬学研究院, 教授 (50359551)
• Project Period (FY): 2021-07-09 – 2024-03-31
• Keywords: グルコサミノグリカン / 分解耐性型アナログ / C-グリコシド / ヒアルロナン / 水素添加反応

Outline of Final Research Achievements

Glycosaminoglycans (GAGs) are long-chain polysaccharides composed of alternating amino sugars and uronic acids. Many of these polysaccharides are found extracellularly and contribute to signal transduction and homeostasis processes. Medium molecular weight GAGs, which are approximately 8-20 sugars long and result from the degradation of GAGs by enzymes in vivo, are known to exhibit length-dependent biological activities. However, the potential for further degradation of medium molecular weight GAGs has limited detailed research. In this study, we aimed to develop medium molecular weight GAG analogs that are resistant to enzymatic degradation while maintaining the structural properties of natural medium molecular weight GAGs. Specifically, we focused on o-HA and established a chemical synthesis method for challenging glycohydrolase-resistant C-glycoside disaccharide analogs.

Free Research Field

生物有機化学

Academic Significance and Societal Importance of the Research Achievements

本研究では、難易度の高いC-グリコシド２糖アナログ合成を実現した。糖同士を炭素で連結するカップリング反応はそれほど例がなく、o-HAを合成できる手法はほとんどなかった。本研究では、o-HAの機能解明やo-HAを基盤とした生物活性分子創製を狙い、様々なC-グリコシド２糖アナログを合成できる手法としたことは学術的に新規性が高く、意義深いものであると考えている。本研究の手法を利用しo-HAアナログの合成が実現できれば、新たな多糖ベースの創薬研究を展開できるため社会的にも意義のあるものと考えている。