Functional analysis of a new glycolipid consists of mannnosyl-oxystearates

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K06976
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47010:Pharmaceutical chemistry and drug development sciences-related
• Research Institution: Kyushu University
• Principal Investigator: Miyamoto Tomofumi 九州大学, 薬学研究院, 准教授 (40182050)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: Mincle / マラセチア / 糖脂質 / アジュバント / グリコシルオキシステアリルマンニトール / 自然免疫

Outline of Final Research Achievements

The Mincle ligand 44-2 discovered by the applicant from the pathogenic fungus Malassezia has 10-O-beta-mannopyranosyloxystearic acid ester-bonded to the 1,3 and 4 of L-mannitol. It is a completely new type of glycolipid. As a result of synthesizing 13 kinds of glycosyloxystearate derivatives based on the structural information of glycolipid 44-2 and evaluating Mincle ligand activity, strong ligand activity of di-beta and di-alfa was confirmed. Based on these findings, five types of esterified compounds having glycerol or mannitol as core alcohol were prepared and the Mincle ligand activity was evaluated. As a result, two mimics of the natural glycolipid 44-2 using D-mannitol as the core alcohol [1,3,4-tri- (di-alfa-D-mannosyl-stearyl) -D-mannitol and 3,4-di- (di-alfa-D-mannosyl-stearyl)-D-mannitol] was confirmed to have a stronger Mincle ligand activity than TDB, so glycosyl-oxystearyl-mannitol has sufficient qualities as an new adjuvant.

Free Research Field

天然物化学

Academic Significance and Societal Importance of the Research Achievements

コアアルコールにD-マンニトールを用いた天然型糖脂質44-2の2種の合成誘導体のMincleリガンド活性は、TDBより強力であり、さらに、TDBがマウス型のMincleに強いリガンド活性を示すのに対し、本研究成果である2種の合成誘導体は、ヒト型Mincleに対してより強いリガンド活性を示すことが明らかとなった。本研究の目的である”マンノシルオキシステアレートの機能解析”に関し、非常に重要な知見が得られ、さらに、これらグリコシルオキシステアリルマンニトールが、ワクチン開発のためのアジュバントとして十分な資質を有することを明らかにしたことの学術的意義及び社会的意義は非常に高い。