The Synthesis and Biological Evaluation of Ligands for C-Type Lectin Receptors

Macrophage inducible C-type lectin (Mincle), expressed on antigen presenting cells (APCs), is an important player in innate immunity due to its capacity to recognise pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), which are involved in pathogen recognition and in tissue homeostasis, respectively. Several ligands can bind Mincle and activate APCs to generate an inflammatory immune response, with prominent examples including the mycobacterial glycolipid, trehalose dimycolate (TDM), and the synthetic analogue thereof, trehalose dibehenate (TDB). Trehalose glycolipids exhibit anti-tumour properties and an ability to switch the phenotype of macrophages from one that is tumour promoting to one that is tumour suppressive. Insomuch, Mincle ligands have potential as adjuvants for both prophylactic and therapeutic (e.g. cancer) vaccines. Maradolipids, which were originally extracted from the nematode Caenorhabditis elegans, are glycolipids containing trehalose with symmetrical or asymmetrical iso-branched and straight chain fatty acids. The incorporation of the iso-branch makes them distinct from linear trehalose diesters (TDEs) and might provide the compounds with enhanced immunomodulatory properties.