Mycobacterium tuberculosis β-gentiobiosyl diacylglycerides signal through the pattern recognition receptor Mincle: total synthesis and structure activity relationships

Mycobacterium tuberculosis H37Ra produces a range of immunogenic beta-gentiobiosyl diacylglycerides. We report the total synthesis of several candidate structures and show that these compounds signal weakly through mouse, but not human, Mincle. Structure-activity relationships reveal a striking dependence upon acyl chain length for gentiobiosyl diacylglyceride signalling through Mincle. Significantly, a truncated beta-glucosyl diglyceride was shown to provide potent signalling through both human and mouse Mincle and could activate murine bone marrow derived dendritic cells.