Precise synthesis of sulfated alternating glycopolymers mimicking physiologically active polysaccharides

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K05605
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 35010:Polymer chemistry-related
• Research Institution: Kyoto Institute of Technology
• Principal Investigator: Minoda Masahiko 京都工芸繊維大学, 分子化学系, 教授 (30229786)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 交互配列ポリマー / グライコポリマー / 硫酸化グライコポリマー / RAFT共重合 / グリコサミノグリカンミミック / コンドロイチン硫酸ミミック / 細胞毒性評価

Outline of Final Research Achievements

A series of alternating glycopolymers mimicking physiologically active polysaccharide, glycosaminoglycans (GAGs), were precisely synthesized based on the controlled radical polymerization. The Principal Investigator have developed a synthetic method to obtain alternating glycopolymers by synthesizing precursor alternating copolymers from unprotected and TMS-protected alkyne groups-substituted vinyl ethers (VE) and maleimides by employing RAFT copolymerization followed by stepwise post-click reactions with two kinds of sugar azides. Examples include the precise synthesis of a GAG mimic with 6-sulfated N-acetylglucosamine (GlcNAc), a GAG mimic with 4- and 6-sulfated GlcNAcs, and an alternating glycopolymer having 3-, 4-, and 6-sulfated GlcNAcs. Analogous alternating glycopolymers with carbohydrate-substituted styrene units were also synthesized. Moreover, it was revealed that all the resulting GAG mimic glycopolymers exhibited no cytotoxicity.

Free Research Field

高分子合成化学

Academic Significance and Societal Importance of the Research Achievements

交互配列ポリマーゆえの機能発現を実証するには、交互配列構造を精密制御すると共に、機能発現に最適な機能基の選択が重要となる。生体機能と関係を持つ天然生理活性多糖であるグリコサミノグリカンは構成単糖が交互配列した構造が特徴であるため、そのミミックとなる交互配列グライコポリマーは、交互配列構造と機能発現との相関を検証するのに最適である。よって、それらの精密合成は学術的に意義を有し、さらに生理活性機能等の発現が達成されれば、有用物質として社会的にも意義深く、応用面での波及効果が期待される。本研究では、硫酸化交互配列グライコポリマーの系統的合成に成功し、バイオメディカル分野等での利用が期待される。