Relationship between chemical structure and adjuvant activity of some synthetic analogues of N-acetyl-muramyl-L-alanyl-D-isoglutamine (MDP).

Synthetic N-acetyl-muramyl-L-alanyl-D-isoglutamine, hereafter referred to as muramyl dipeptide or MDP, represents the minimal structure which can replace mycobacterial cells in Freund's complete adjuvant. This synthetic adjuvant can also enhance the humoral antibody response when administered to mice with an antigen in water by various routes including the oral route. The present paper reports some new results concerning the relationship between the structure and the adjuvant activity of MDP. Synthetic analogues of MDP were tested either in a water-in-oil emulsion in guinea-pigs or in saline in mice. The chemical modifications concerned essentially the D-glutamyl residue. The results obtained confirm the importance of maintaining the intact structure of the D-Glu residue and show that adjuvant activity can be abolished by certain modifications at the level of both carboxyl functions.