Muramyl Dipeptide

Ichiro Azuma and Tsuyoshi Otani, Institute of Immunological Science, Hokkaido University, Sapporo, Japan

Heat-killed mycobacterial cells suspended in mineral oil (so-called Freund's complete adjuvant, FCA) provide one of the most potent immunoadjuvant for the induction of cell-mediated immunity and humoral antibody formation. In 1971, Azuma showed that the cell wall fraction was the major active component for the immunopotentiating activity of mycobacterial cells. The peptidoglycan portion was shown to be the most important for the immunoadjuvant activity of mycobacterial cell wall. In 1974, the minimum essential structure required for the immunoadjuvant activity in the peptidoglycan was defined independently as an JV-acetylmuramyl-L-alanyl-D-isoglutamine (MDP, muramyl dipeptide; Figure 1) by the groups of E. Lederer and S. Kotani. Several hundred derivatives and related compounds of MDP have been synthesized chcmically and their immuno-pharmacological activities and structure-activity relationships have been investigated (Figure 2). MDP is established as the adjuvant-active component not only of mycobacterial cells but also of other bacterial cell walls.

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