Trehalose diesters containing a polar functional group-modified lipid moiety: Synthesis and evaluation of Mincle-mediated signaling activity

Takanori Matsumaru, Kodai Sueyoshi, Kana Okubo, Shusuke Fujii, Kasumi Sakuratani, Ryota Saito, Kazunari Ueki, Sho Yamasaki, Yukari Fujimoto

Research output: Contribution to journalArticlepeer-review

Abstract

Mincle, a C-type lectin receptor (CLR), activates the innate immune system by recognizing certain complex lipid compounds. In this study, we designed and synthesized trehalose disteate (TDS) and dibehenate (TDB), containing a polar-functional group in the middle of fatty acid moieties, based on a model of the Mincle–glycolipids interaction. The modified fatty acids were prepared using hydroxy fatty acids as common intermediates, and conjugated with an appropriate trehalose moiety to synthesize the desired trehalose diesters. TDE derivatives containing the modified fatty acid have different Mincle-mediated signaling activities depending on the position of the functional group and the length of the lipids. The newly developed TDE derivatives exhibit signaling activity comparable or superior to that of TDS or TDB, and the results suggest that Mincle tolerates polar functional groups at a certain position of the lipid chain of TDE. The introduction of the polar functional groups into the lipid moiety of the glycolipids also resulted in improved solubility in polar solvents, which would be advantageous for various analyses and applications.

Original languageEnglish
Article number117045
JournalBioorganic and Medicinal Chemistry
Volume75
DOIs
Publication statusPublished - 2022 Dec 1

Keywords

  • C-type lectin receptor
  • Glycolipid
  • Innate immunity
  • Mincle
  • Trehalose diester

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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