Syntheses of phosphatidyl-β-d-glucoside analogues to probe antigen selectivity of monoclonal antibody ‘DIM21’

Herein, we report the chemical syntheses of a series of phosphatidyl-β-d-glucoside (PtdGlc) analogues, including 6-O-Ac, sn-2-O-Me, phosphorothioate as well as phosphatidylgalactoside and -mannoside derivatives. In the key step, β-glycosyl H-phosphonate was condensed with enantiomerically pure diacylglycerol. Comparison of spectroscopic data with mono-acetylated PtdGlc from natural source confirmed the presence of an acetyl moiety at position 6. Furthermore, the reactivity of PtdGlc and its analogues toward monoclonal antibody ‘DIM21’ (MAb DIM21) was evaluated, revealing the crucial structural antigen features for successful MAb DIM21 binding.

Chemical synthesis of phosphatidyl-β-d-glucoside (PtdGlc) and its analogues was achieved. The proposed structure of natural 6-O-Ac PtdGlc was confirmed. The reactivity of monoclonal antibody ‘DIM21’ towards PtdGlc and its analogues were mapped.Figure optionsDownload as PowerPoint slide