TY - JOUR
T1 - Fungal β-Mannosyloxymannitol Glycolipids and Their Analogues
T2 - Synthesis and Mincle-Mediated Signaling Activity
AU - Matsumaru, Takanori
AU - Sakuratani, Kasumi
AU - Yanaka, Saeko
AU - Kato, Koichi
AU - Yamasaki, Sho
AU - Fujimoto, Yukari
N1 - Funding Information:
This work was partly supported by JSPS KAKENHI under Grants JP17H02207, JP18H04426, JP19H04815, JP17H05800, JP20K05733 and JP21H04709; by AMED under Grants JP18ae0101052; by Takeda Science Foundation; and by The Mitsubishi Foundation. A part of this work was conducted in Institute for Molecular Science, supported by Nanotechnology Platform Program “Molecule and Material Synthesis” (JPMXP09S20MS0024) of the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan.
Publisher Copyright:
© 2022 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
PY - 2022/5/25
Y1 - 2022/5/25
N2 - Mincle, a C-type lectin receptor (CLR), senses certain lipid conjugates, leading to the activation of the innate immune system. The lipid conjugate ligands include glyco-, glycero-, and mannitol lipids. Recently, a fungal β-mannosyloxymannitol glycolipid demonstrating a novel architecture, “44-2,” was isolated from the fungus Malassezia and displayed potent Mincle-mediated signaling activity. For this study, we synthesized the diastereomeric pair of mannosyloxymannitol glycolipids and their analogues and analyzed the structure-activity relationships of Mincle-mediated signaling. The results suggest that the dimannosyl-fatty acid moiety in the mannosyloxymannitol glycolipid-type structure plays a major role in the molecular recognition of Mincle.
AB - Mincle, a C-type lectin receptor (CLR), senses certain lipid conjugates, leading to the activation of the innate immune system. The lipid conjugate ligands include glyco-, glycero-, and mannitol lipids. Recently, a fungal β-mannosyloxymannitol glycolipid demonstrating a novel architecture, “44-2,” was isolated from the fungus Malassezia and displayed potent Mincle-mediated signaling activity. For this study, we synthesized the diastereomeric pair of mannosyloxymannitol glycolipids and their analogues and analyzed the structure-activity relationships of Mincle-mediated signaling. The results suggest that the dimannosyl-fatty acid moiety in the mannosyloxymannitol glycolipid-type structure plays a major role in the molecular recognition of Mincle.
KW - C-Type lectin receptor
KW - Innate immunity
KW - Lipid conjugates
KW - Mincle
KW - Natural products
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U2 - 10.1002/ejoc.202200109
DO - 10.1002/ejoc.202200109
M3 - Article
AN - SCOPUS:85130609904
SN - 0365-5490
VL - 2022
JO - Justus Liebigs Annalen der Chemie
JF - Justus Liebigs Annalen der Chemie
IS - 20
M1 - e202200109
ER -