N-acetyl-D-Muramic acid

Murein Bacterial cell wall N-acetyl-D-Glucosamine + N-acetyl-D-Muramic acid pi,4 ... 

The major component of all known bacterial cell walls is a polysaccharide composed of Af-acetyl-D-glucosamine (NAG) linked together by 8-(l— 4) glycosidic bonds, as in chitin, but with every other NAG residue substituted at C-3 by an ether linkage to the hydroxyl group of L-lactic acid to give N-acetyl-D-muramic acid (NAM) [85,86,87,88]. This results in a nine-... 

Biosynthesis of Eight- and Nine-Carbon Sugars N-Acetyl-D-Neuraminic Acid, N-Acetyl-o-Muramic Acid, and 2-Keto-3-Deoxy-D-Mannooctulosonic Acid (KDO)... 

Biosynthesis of N-acetyl-D-muramie acid by N-acetyi-D -muramic acid synthase... 

Fig. 1 shows the structure of the monomer of the peptidoglycan of Mycobacteria N-acetyl D-glucosamine is linked to N-glycolyl muramic acid (2) which carries a diamidated tetrapeptide L-Ala-D-isoGln-wc,vo-DAP-D-Ala. 

In the biosynthesis of A. s., the amino group is supplied by transamination from glutamine. Fructose 6-phosphate is aminated to D-glucosamine 6-phosphate by a hexose-phosphate transaminase. Glucosamine phosphate can then be converted by a transacetylase into the N-acetyl derivative. The latter is isomerized to the 1-phosphate, then activated by reaction with UTP, to form UDP-N-acetylglucosamine, which can be isomerized to UDP-N-acetylgalactosamine. See Muramic acid. Neuraminic acid. 

Cycloserine (Fig- 4) is produced by several species of Streptomyces. One of the basic glycosyl components of the bacterial cell wall, n-acetyl-muramic acid (the product of Mur A and MurB), is modified by the addition of the first three amino acids sequentially by MurC, MurD and MurE enzymes. A dipeptide, D-alanyl-D-alanine is then added to make the pentapeptide. In bacteria, L-alanine is the native form and it is converted to D-alanine form by alanine racemase (Air). Two D-alanines are joined by D-ala-D-ala ligase (DdlA) to synthesize the dipeptide. Cycloserine resembles the substrate for Air and Ddl and inhibits their respective reactions in stage I of the peptidoglycan biosynthesis (Fig. 2). 

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). 

N-Acetyl muramic acid [NAMA, / -2-(acetylamino)-3-O-(l-carboxyethyl)-2-deoxy-D-... 

L-Alanine 9 D-Glutamate 0 L-Lysine O Glycine O D-Alanine Mur NAc = N-Acetyl-muramic acid... 

In the synthesis of N-acetyl-muramyl-peptides, and obviously of MDP, the most frequently used protected muramyl derivative is 1-O-benzyl-4,6-O-benzylidene-N-acetyl-muramic acid. This allows the mild and possibly simultaneous elimination of the benzylidene group and the benzyl group. Starting from D-glucosamine, either a- or p-benzyl-4,6-0-benzylidene-N-acetyl-muramide can be obtained (Fig. 4) 17, 25, 53). In spite of its slower hydrogenolysis rate 44), the a-isomer which is easier to prepare is generally preferred (55, 44) to the p-isomer 50). 

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