Abstract Plant-derived 6-O-acylated steryl β-glucosides (βASGs) were investigated as ligands of the C-type lectin receptor Mincle to elucidate their structure–activity relationships. Evaluation of a synthetic monosaccharide βASG library demonstrated that βASGs generally act as Mincle agonists, whereas the deacylated analogue was inactive, indicating an important role for the fatty acyl moiety. Both acyl and sterol structures strongly governed activity, with cholesterol-containing analogues suggesting a relative enhancement toward human Mincle. A comparison of Mincle-mediated signaling activity between βCAG and its α-anomer, Helicobacter pylori-derived cholesteryl 6-O-acyl-α-glucoside (αCAG), showed that αCAG was more potent, pointing to a potential preference of Mincle for certain bacterial glycolipid structures.
Yoshida et al. (Mon,) studied this question.