N-acetyl-muramyl-L-alanyl-D-isoglutamine

The structure of the native immunostimulatory MDPs was found to be n-acetyl muramyl-L-alanyl-D-isoglutamine (N-acetyl muramic acid is a base component of bacterial peptidoglycan). Native TDM is a potent pyrogen and is too toxic for general use as an adjuvant. The molecular basis underlying MDP s adjuvanticity remains to be fully elucidated. Administration of MDP is, however, known to activate a number of cell types which play direct/indirect roles in immune function, and induces the secretion of various immunomodulatory cytokines (Table 10.23). 

MDP muramyl dipeptide (N-acetyl-muramyl-L-alanyl-D-isoglutamine) WSA Water Soluble Adjuvant AL multi-poly-D, L-alanyl-poly-L-lysine... 

Further degradation of low molecular weight fractions obtained from lysozyme digestion of cell walls then led to the conclusion that an N-acyl muramyl dipeptide should be the minimal adjuvant active structure (small square frame of Fig. 2). And indeed, N-acetyl-muramyl-L-alanyl D-isoglutamine (1) first synthesized by Merser et al. (49, 50) was found to be fully active (16). Kotani et al. (29, 30) independently came to the same conclusion. 

Recently, a modified procedure was employed giving 4,6-0-anisylidene-N-acetyl-muramyl-L-alanyl-D-isoglutamine. The single blocking group was easily removed with 60% acetic acid at room temperature (35). 

Fig. 5. Synthesis of [6- H)-N-acetyl-muramyl-L-alanyl-D-isoglutamine IS) References, pp. 38—47...

Thus (77) 47) is a dimeric derivative of N-acetyl-muramyl-L-alanyl-D-isoglutamine-L-lysine [MDP-Lys, (63)], in which the e-amine functions of each monomeric glycotripeptide unit are linked by an adipimidyl residue, the coupling being achieved by means of dimethyl adipimidate 23. 48). 

Adam, A., M. Devys, V. Souvannavong, P. Lefrancier, and E. Lederer Correlation of structure and adjuvant activity of N-acetyl-muramyl-L-alanyl-D-isoglutamine (MDP), its derivatives and analogues. Anti-adjuvant and competition properties of stereoisomers. Biochem. Biophys. Res. Comm. 72, 339 (1976). 

Hasegawa, a., Y. Kaneda. M. Amano, M. Kiso, and I. Azuma A facile Synthesis of N-acetyl-muramyl-L-alanyl-D-isoglutamine and its Carbohydrate Analogs and their Immunoadjuvant Activities. Agric. Biol. Chem. 42, 2187 (1978). 

Kusumoto. S.. S. Okada. and T. Shiba Synthesis of 6-O-mycoloyI-N-acetyl-muramyl-L-alanyl-D-isoglutamine with immunoadjuvant activity. Tetrahedron Lett. 4287 (1976). 

LEFRANaER, P.. J. Choay. M. Derrien, and I. Lederman Synthesis of N-acetyl-muramyl-L-alanyl-D-isoglutamine, an adjuvant of the immune response and of some N-acetyl-muramyl-peptide analogs. Int. J. Peptide Protein Res. 9, 249 (1977). 

Parant, M., C. Damais, F. Audibert, F. Parant, L. Chedid, E. Sache, P. Lefrancier, J. Choay, and E. Lederer In vivo and in vitro stimulation of non specific immunity by the p-D-p-amino-phenyl glycoside of N-acetyl-muramyl-L-alanyl-D-isoglutamine and an oligomer prepared by cross-linking with glutaraldehyde. J. Infec. Dis. 138, 378... 

Reichert, C. M., C. Carreu, M. Jolivet, F. Audibert, P. Lefranoer. and L. Chedid Synthesis of N-acetyl-muramyl-L-alanyl-D-isoglutamine (MDP) containing conjugates and their use as a hapten-carrier system Mol. Immunol. 17, 357 (1980). 

SouvANNAvoNG, V., A. Adam, and E. Lederer Kinetics of the humoral and cellular immune response of guinea pigs after injection of the synthetic adjuvant N-acetyl-muramyl-L-alanyl-D-isoglutamine comparison with Freund complete adjuvant. Infect. Immun. 19, 966 (1978). 

Kotani, S., Y. Watanabe, F. Kinoshita, I. Morisaki, K. Kato, T. Shiba, S. Kusumoto, Y. Tarumi, and K. Ikenaka The effect of replacement of L-alanine residue by glycine, L-serine or D-alanine in an N-acetyl muramyl-L- alanyl-D-isoglutamine on immunoadjuvanticities of molecules. Biken J. 20, 39 (1977). 

Chedid, L., M. Parant, F. Parant, P. Lefrancier, J. Choay,andE. Lederer Enhancement of non-specific immunity to Klebsiella pneumoniae infection by a synthetic immuno-adjuvant (N-acetyl-muramyl-L-alanyl-D-isoglutamine) and several analogs. Proc. Natl. Acad. Sci. 74, 2089 (1977). 

Damais, C., M. Parant, L. Chedid, P. Lefrancier, and J. Choay In vitro spleen cell responsiveness to various analogs of MDP(N-acetyl-muramyl-L-alanyl-D-isoglutamine), a synthetic immunoadjuvant, in MDP high-responder mice. Cell. Immunol. 35, 173 (1978). 

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