Lipid length and iso-branching of trehalose diesters influences Mincle agonist activity. Issue 12 (22nd March 2018)

• Record Type: Journal Article
• Authors: Khan, Ayesha; Kodar, Kristel; Timmer, Mattie S.M.; Stocker, Bridget L.
• Is Part Of: Tetrahedron. Volume 74:Issue 12(2018)
• Page Start: 1269
• Page End: 1277
• Publication Date: 2018-03-22
• Subjects: Glycolipid -- Trehalose -- Iso-branched fatty acid -- Macrophage -- Mincle; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tet.2017.11.076
• Languages: English
• ISSNs: 0040-4020

Abstract

Abstract: We report on the efficient synthesis of linear trehalose diesters (TDEs) and iso-branched TDEs (maradolipids or iso-TDEs) and their ability to activate bone marrow-derived macrophages (BMDMs) as determined by cytokine (IL-1β, IL-12, IL-6, IL-10) and chemokine (MIP-2) production. Both classes of TDEs were found to activate BMDMs in a Mincle-dependent manner, with longer-chain (≥C18) lipids leading to a robust inflammatory response. On the whole, the iso-branched TDEs led to greater cytokine production and a faster immune response when compared to their linear counterparts. Moreover, C12-TDE and iso-C12-TDE elicited the production of MIP-2 by BMDMs, thereby providing the first example of TDEs with a chain length of ≤ C12 leading to a Mincle-dependent immune response and one that is less inflammatory in nature. Graphical abstract: