N-acetylmuramyl-dipeptide

Lyons, K.C., Charman, W.N., Miller, R. and Porter, C.J.H. (2000) Factors limiting the oral bioavailability of N-acetylglucosaminyl-N-acetylmuramyl dipeptide (GMDP) and enhancement of absorption in rats by delivery in a water-in-oil microemulsion. Int. J. Pharm., 199, 17-28. 

A similar effect has been reported if peptides, even if self-antigens such as the hormone LHRH, are linked covalently to other well established lmmunoadjuvants, e.g. to the muramyl-dipeptide. In fact, with a N-acetylmuramyl-dipeptide/LHRH construct immunological castration of male mice was achieved (170-173). The identical effect has recently been obtained with a N-acetylmuramyl-dipeptide/LHRH construct linked to a solubilized polymer support (131). We have attempted this approach with the self-antigen gastrin. In order to exploit the... 

Upon immunization of rabbits with these conjugates no Immune response could be observed at least in terms of detectable antl-gastrln antibodies. The question arises of whether the immunological castration induced with the covalent N-acetylmuramyl-dipeptide/LHRH adduct derives from an immune response to the hormone or from occupancy of the LHRH receptor containing cells with immunoadjuvant moieties and correspondingly, from an immune response to these cells. 

Yamamura, Y., I. Azuma, K. Sugimura, M. Yamawaki, M. Uemiya, S. Kusumoto, S. Okada, and T. Shiba Immunological and antitumor activities of synthetic 6-O-mycoloyl-N-acetylmuramyl dipeptides. Proc. Japan Acad. 53, 63 (1977). 

UDP-N-acetylmuramic acid. The enzymes involved are highly specific, and the sequence of the amino acids is determined solely by the substrate and acceptor specificities of these enzymes, which require a divalent cation and ATP. One exception to the rule of sequential addition is the terminal dipeptide sequence, D-alanyl-D-alanine this dipeptide is first assembled and then transferred to the UDP-N-acetylmuramyl-tripeptide (see Scheme 2). 

Heymer, B., H. Finger, and C. H. Wirsing Immunoadjuvant effects of the synthetic muramyl dipeptide (MDP) N-acetylmuramyl-L-alanyl-D-isoglutamine. Zeit.-Immuni-tatforsch. 155, 87 (1978). 

N -[ N-P -Acetylmuramoyl) -L-alanyl]-D-a-glutamine, 9CI. N-Acetylmuramyl-L-alanyl-D-isoglutamine. Muramyl dipeptide. MDP... 

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