There is a pressing need for the development of novel adjuvants for human use.The minimal bioactive structure of bacterial peptidoglycan (PGN), muramyl dipeptide (MDP) and its derivative murabutide ...(MB), have long been known for their adjuvant activities. For this reason, a series of novel desmuramyl dipeptides have been designed and synthesized as part of our search for therapeutically useful MDP analogues. Since nucleotide oligomerization domain 2 (Nod2) is a putative receptor for MDP, we used engineered HEK293 cells overexpressing Nod2 to screen and validate our compounds for their Nod2-agonist activity. Their immunomodulatory properties were subsequently assessed in vitro, by evaluating their effect on proinflammatory cytokine production of phorbol 12-myristate 13-acetate (PMA)/ionomycin-stimulated human peripheral blood mononuclear cells (PBMC). Herein, we present novel desmuramyl dipeptides, the most active of them possessing immunoenhancing properties as a result of their potent Nod2-agonistic effect.
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