N-Acetyl-muramic acid

Also in the PP, associated with the CM, one can find the murein sacculus (for a review see [8]). This network is formed by the macromolecule pepti-doglycan, which confers the characteristic cell shape and provides the cell with mechanical protection. Peptidoglycans are unique to prokaryotic organisms and consist of a glycan backbone of N-acetylated muramic acid and N-acetylated glucosamine and cross-linked peptide chains [9-13]. 

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-... 

Lysozyme catalyzes the hydrolysis of a polysaccharide that is the major constituent of the cell wall of certain bacteria. The polymer is formed from /3( 1 —> 4)-linked alternating units of IV-acetylglucosamine (NAG) and N-acetyl-muramic acid (NAM) (Figure 1.25). The solution of the structure of lysozyme... 

Add (pick) saccharide residues from the list of aldoses (hexoses in al-dopyranose form, pentoses in aldofuranose form, and tetraoses in open-chain form), ketoses (hexoses in ketofuranose form, pentoses and tetraose in open-chain form), derivatives (glucosamine, galactosamine, N-acetylnuraminic acid, N-acetyl muramic acid, inositol, 2-deoxyribose, rhamnose, fucose, and apiose), and blocking groups (H, NH2, =0, COO—, methyl, lactyl, O-methyl, iV-methyl, O-acetyl, iV-acetyl, phosphoric acid, sulfate, iV-sulfonic acid) to build polysaccharides. 

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

Abbreviations NAM, N-acetyl muramic acid NAG, N-acetyl glucosamine GA, glucosamine G, glucose... 

The sub-sites involved in binding of the lysozyme substrates do not have equivalent affinities for the two types of hexopyranosyl residues present. Thus, the binding of N-acetyl glucosamine or N-acetyl muramic acid residues is favored at certain sites and forbidden at others and since... 

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). 

The preparation of 4,6-O-anisylidene-N-acetyl-muramic acid, without protection at C-1, but bearing an easily removable blocking group at C-4 and C-6, was reported (55). Recently, l-a-benzyl-4,6-0-isopropyli-dene-N-acetyl-muramide has been prepared 20). 

Some analogues in which N-acetyl-muramic acid is replaced by another carbohydrate have been reported. 

Many derivatives of MDP have been described in which the hydroxyl groups of muramic acid, especially the primary hydroxyl, are substituted in the following only details of the preparation of suitably protected N-acetyl-muramic acid derivatives will be discussed. 

Compound (48), 6-O-mycoloyl-MDP results from acylation of the primary hydroxyl group with natural mycolic acid isolated from mycobacterial cells. Its synthesis is illustrated in Fig. 6 (34, 66). The key intermediate (a), a partially protected N-acetyl-muramic acid derivative, can be substituted by a tosyl group at C-6, which can be exchanged with the potassium salt of the mycolic acid in the presence of 18-crown-6 following the method of Polonsky etal. (58). This mild acylation procedure avoids the use of the acid chloride or trifluoracetic anhydride method, which cannot be applied in the present instance because of the presence of a P-hydroxyl group in mycolic acid. The penta-... 

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