Evaluation of the effect of natural or unnatural glycosylation modes on the activity of glycoproteins

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K18215
• Research Category: Grant-in-Aid for Challenging Research (Pioneering)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 37:Biomolecular chemistry and related fields
• Research Institution: Osaka University
• Principal Investigator: Kajihara Yasuhiro 大阪大学, 大学院理学研究科, 教授 (50275020)
• Co-Investigator(Kenkyū-buntansha): 和泉 雅之 高知大学, 教育研究部総合科学系複合領域科学部門, 教授 (80332641) ; 松尾 一郎 群馬大学, 大学院理工学府, 教授 (40342852)
• Project Period (FY): 2021-07-09 – 2024-03-31
• Keywords: 糖鎖 / 糖タンパク質 / 水和

Outline of Final Research Achievements

We hypothesized that glycans regulate the dynamic behavior of water and enhance protein-protein interactions. Therefore, we investigated the interaction between glycans and water, as well as protein-protein interactions. We synthesized several glycoproteins and then used it for the investigation of the interaction between glycoprotein and water by hydrogen-deuterium exchange mass spectrometry and the binding affinity by surface plasmon resonance. As a result, it was found that glycans interacted with water higher than that of proteins. Comparing proteins with and without glycans, the affinity of glycoprotein for the receptor was 2 times higher than that of non-glycosylated proteins. There was no difference in affinity for the receptor between the native and haloacetamide forms of the glycoproteins.

Free Research Field

生物有機化学

Academic Significance and Societal Importance of the Research Achievements

タンパク質やペプチドは創薬に広範囲に利用されている。その際、ヒトの体内と同様糖鎖が結合することで、タンパク質、ペプチドの薬効、安定性、血中寿命が長くなることがわかっている。また、抗体医薬のように糖鎖が必須の分子が多い。しかし、その糖鎖が必要な理由は、はっきりしないまま糖鎖が使われている。本研究は糖鎖機能を示す新しい研究成果になったと考えている。