GlcC14C18 is a synthetic C6-branched glycolipid that activates the macrophage-inducible C-type lectin (Mincle) receptor.
This glucose monoester was developed using a rational design to obtain a structurally simple molecule that binds and activates both human and murine Mincle [1].
GlcC14C18 recognition by Mincle leads to the phosphorylation of the immunoreceptor tyrosine activation motif (ITAM) of the Mincle-associated Fc receptor common γ-chain (FcRγ), and subsequent Syk-CARD9 signaling and NF-κB activation. Mincle triggering ultimately results in the production of Th1/Th17 polarizing cytokines and chemokines [1-3].
GlcC14C18 displays similar activity to two other extensively studied Mincle agonists: the trehalose-6,6-dimycolate (TDM, also known as cord factor) naturally found in the cell wall of Mycobacterium tuberculosis, and its synthetic analog, trehalose-6,6-dibehenate (TDB) [1].
Importantly, GlcC14C18 displays less toxicity on human monocytes and monocyte-derived dendrictic cells in vitro than TDB [1].
References:
- Decout A. et al., 2017. Rational design of adjuvants targeting the C-type lectin Mincle. PNAS. 114(10):2675-80.
- Patin EC. et al., 2017. Macrophage Inducible C-Type Lectin As a Multifunctional Player in Immunity. Front Immunol. 8:861.
- Williams SJ., 2017. Sensing Lipids with Mincle: Structure and Function. Front Immunol. 8:1662.