Muramyl Dipeptide and its Derivatives: Peptide Adjuvant in Immunological Disorders and Cancer Therapy

Muramyl dipeptide (MDP) is a synthetic immunoreactive peptide consisting of N-acetyl muramic acid attached to a short amino acid chain of L-Ala-D-isoGln. It was first identified in bacterial cell wall peptidoglycan as an active component in Freund's complete adjuvant. In the cell, MDP is detected by NOD2, a cytoplasmic receptor belonging to the human innate immune system. NOD2 mutations are frequently observed in patients with Crohn's disease, an autoimmune disorder, suggesting the significance of the MDP-NOD2 pathway in activating immunity. For this reason, structural modifications of MDP and its derivatives have been extensively studied in an attempt to increase adjuvant activity and boost the immune response effectively for clinical use in the treatment of cancer and other diseases. This review summarizes the synthetic chemistry of MDP and its derivatives and discusses their pharmacological action and stereoselective synthesis.