Development of alpha-GalCer Analogues with an alpha-Fluorocarbonyl Moiety as Th2-Selective Ligands of CD1d

摘要

A series of alpha-GalCer analogues containing an alpha-fluorocarbonyl moiety at the terminal position of the acyl chain were designed for targeting polar residues in the hydrophobic cavity of CD1d using a structure-based approach. The acyl chain length was efficiently adjusted by an asymmetric alkyne-alkyne cross coupling strategy, and the newly synthesized alpha-GalCer analogues showed the high Th2-selective activity of iNKT cells. The biased activity of ligands could be caused by the hydrogen-bonding interaction between ligands and CD1d according to the Th2-selective cytokine secretion and molecular docking studies.