Novel lipid A mimetics derived from pentaerythritol: synthesis and their potent agonistic activity

A pentaerythritol unit is substituted for glucosamine as its functional mimic at the reducing end of lipid A disaccharide. Two such pentaerythritol derived lipid A mimetics and , carrying three identical fatty acyl moieties, have been designed and synthesized. An efficient strategy, which involves simultaneous introduction of lipids onto two amino groups, is described for the synthesis of compounds and . The biological activity profile of these two novel lipid A mimetics and is surprisingly similar to the natural lipid A product isolated from Salmonella minnesota R595. An in vitro cell activation assay, using human adherent antigen presenting cells, has demonstrated that both and induce the secretion of high levels of cytokines such as tumour necrosis factor-α (TNF-α), IL-6 and IL-8. Also, in a totally synthetic liposomal vaccine system, and exhibit strong immunostimulatory adjuvant property in enhancing antigen specific T-cell activation.