IV-Acetylmuramic acid

Lysozyme hydrolyses a polysaccharide present in bacterial cell walls that is a / -(l—>4) linked polymer of alternating IV-acetylmuramic acid (NAM) and N-acetylglucosamine (NAG) residues. The enzyme only attacks the NAM—>NAG linkage. Certain lysozymes also attack chitin, the / -(l- 4) linked linear polymer of NAG (9). It was demonstrated by Rupley (5), using oligosaccharides of NAG, that the Ci-O linkage was specifically cleaved and / -configuration was retained. 

Scheme 2, Biosynthesis of UDP-IV-acetylmuramyl-pentapeptide. (MurNAc = IV-acetylmuramic acid, PEP = enolpyruvate phosphate.)...

A-Acetylmuramic acid (D-MurpAc) HO COOH NHCOCH3 iV-Acetylmuramic acid is 2-acetamido-2-deoxy-3-0-[(R)-l-carboxyethyl]-D-glucose. MurAc and GlcNAc alternate via P-1 4 linkages in murein (peptidoglycan) of bacterial ceU wall. 

The anomers 65, containing the intercalator and carbohydrate moieties of the endiyne antibiotic neocarzinostatin, were synthesized from 2-amino-2-deoxy-D-galactose. They were shown to cleave DNA under photoirradiation (365 nm), but with a different site selectivity from that of neocarzinostatin. A multi-gram synthesis of UDP-iV-acetylmuramic acid was made possible by an improved synthesis of the 1-phosphate precursor. ... 

Ribosylation of isopropylideneuridine and subsequent manipulations led to the synthesis of 170 (R = H), which constitutes a part-structure of the liposidomycin class of antibiotics. The two isomers of 170 (R = CH2OH) were also prepared in synthetic sequences that involved ribosylation of D-allofuranose and L-talofuranose derivatives at 0-5, with introduction of uracil at a late stage. Molecular modelling was carried out of both liposidomycins and tunicamycin with the UDP-iV-acetylmuramic acid-pentapeptide that is the substrate for the enzyme (translocase) in bacterial cell wall biosynthesis that the antibiotics inhibit, and, in accordance with the predictions, only the 5-isomer of 170 (R = CH2OH) was a good inhibitor. ... 

UDP-iV-acetylmuramic acid UDP-A-acetylmuramyl peptides UDP-X-acetylgalactosamine 4-sulfate... 

Of significance are D-glucosamine and D-mannosamine (Fig. 29). d-G1ucos-amine-6-phosphate is formed from fructose-6-phosphate by the pathway given in Fig. 32. It is subsequently transformed to iV-acetylglucosamine-6-phosphate and iV-acetylmuramic acid. Synthesis of D-glucosamine-6-phosphate includes an intramolecular oxidoreduction at positions 1 and 2 transforming the ketose to an aldose derivative. 

The carbohydrate chains of the peptidoglycan consist of up to twelve alternating iV-acetylglucosamine and iV-acetylmuramic acid units (D 1.1) linked to each other through 8-1,4-bonds. The muramic acid residues are either wholly or partly substituted by peptide chains which may consist of L-alanine, D-glutamic acid. 

Glycosidases, e.g., lysozyme, destroy the bonds between the iV-acetylglucos-amine and iV-acetylmuramic acid residues of the peptidoglycan allowing the UDP-activated precursors to add to the points of breakage with loss of UDP (C 6). The amino acid chain of the incorporated iV-acetylmuramyl peptide is coupled with the peptide chain of another iV-acetylmuramine moiety by trans-peptidation. The bond between the terminal D-alanyl residues is cleaved and a new bond is formed interlinking both peptide chains. The last D-alanyl moiety of the precursor peptide is lost in this reaction. 

Lysozyme is an important enzyme that catalyzes the hydrolysis of a polysaccharide that is the major constituent of the cell wall of certain bacteria. The polymer is formed from j8(l 4) linked alternating units of iV-acetyl-glucosamine (NAG) and iV-acetylmuramic acid (NAM) (Fig. 4.5). 

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