2022 Fiscal Year Final Research Report

Elucidation of unresolved anti-HIV mechanism of sulfated polysaccharides

Research Project

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Project/Area Number	20K05612
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 35020:Polymer materials-related
Research Institution	Kitami Institute of Technology
Principal Investigator	Yoshida Takashi 北見工業大学, 工学部, 特任教授 (40166955)
Co-Investigator(Kenkyū-buntansha)	浅井大輔昭和薬科大学, 薬学部, 准教授 (10423485) 宮崎健輔北見工業大学, 工学部, 准教授 (50636610)
Project Period (FY)	2020-04-01 – 2023-03-31
Keywords	硫酸化糖鎖 / 硫酸化アルキルオリゴ糖鎖 / ウイルス表皮タンパク質 / オリゴペプチド / 表面プラズモン共鳴（SPR）装置 / 動的光散乱（DLS）装置
Outline of Final Research Achievements	Electrostatic interactions of oligopeptides from virus envelope glycoproteins with sulfated polysaccharides were investigated using SPR and DLS measurements. Sulfated polysaccharides interacted ionically with clustered and concentrated regions of basic amino acids on the envelope glycoproteins to prevent the infections to cells. Acidic and bulky amino acids inhibit in the electrostatic interactions. Sulfated 1-alkyl-triazole-maltoheptaosides having potent anti-HIV activity were synthesized and subjected to SPR with liposomes to elucidate the cytotoxic mechanism. Nonsulfated and sulfated 1-alkyl-triazole-maltoheptaosides bearing a C18 alkyl chain showed the highest apparent association-rate constant and lowest dissociation-rate constant against liposomes, indicating that the alkyl groups bearing longer-chains interact tightly with the liposomes. The results suggest that the longer-chain alkyl groups penetrate into the lipid bilayer of MT-4 cells to induce cytotoxicity.
Free Research Field	高分子材料関連
Academic Significance and Societal Importance of the Research Achievements	ウイルス表皮タンパク質中の感染に関係する領域のオリゴペプチドを合成し硫酸化糖鎖との相互作用をSPRやDLS装置を用いて測定し明らかにした。硫酸化アルキルオリゴ糖鎖の高い抗HIV性における長鎖アルキル鎖の役割は、ウイルスや細胞のモデルとしてリポソームとの相互作用をSPR、DLS、高分解能NMRなどにより定量的に調べた。硫酸化糖鎖、硫酸化アルキルオリゴ糖鎖のHIV、デング熱ウイルス、インフルエンザウイルスなどの抗ウイルス活性発現メカニズムや細胞毒性メカニズムが明らかになり学術的意義は高い。また、ウイルス吸着性能を持つ不織布マスクやフィルター、生医学材料への応用も期待され社会的意義もある。