The outer membrane of the enterobacterial cell wall harbours structurally conserved glycolipid and extended oligosaccharide domains being responsible for endotoxic and manifold immunomodulating activities ranging from beneficial effects up to life-threatening septic shock. Current advances in the field covering the TLR4/MD-2 interaction with novel lipid A mimetics revealed a fertile synthetic playground to induce agonistic and antagonistic activities upon lipopolysaccharide (LPS) stimulation. In addition, chemical synthesis of the Kdo and oligoheptosyl region provides ligands allowing powerful insight on a molecular basis into specific and relaxed binding modes with anti inner-core antibodies as well as bacterial and mammalian lectins. A comprehensive understanding of these LPS-protein interactions should thus allow for a rational design of urgently needed improvements in diagnostics and therapies of acute and chronic bacterial infections.
