MODULATION OF MOLECULAR RECOGNITION AND BIOACTIVITIES OF IMMUNOSTIMULATORY GLYCOLIPIDS BY LIPID CHAIN MODIFICATION WITH POLAR FUNCTIONAL GROUP

摘要

Various bacterial membrane glycolipids are recognized by innate immune receptors such as TLRs, and lipid antigen-presenting molecules, CD1a-d. These proteins activate immune system and lead to release of various proinflammatory cytokines. These proinflammatory cytokines activate adaptive immunity to affect other immune cells. The recognition of lipid moieties by the lipid recognition proteins, such as TLR2, TLR4 and CD1a-d, is conducted by extensive hydrophobic pocket. We focused on a few polar residues in the hydrophobic pocket of lipid recognition receptors, because these shielded hydrogen-bond in hydrophobic pocket has been shown to be relatively stable!12]. We thus designed the ligands containing polar functional groups in the lipid chain, which were expected to interact with the hydrophilic regions of the binding pocket, in order to improve activity and selective activation of lipid recognition receptors.