UDP-MurNAc-L-Ala

The substrate for MurD (UDP-MurNAc-L-Ala) and purified Mur enzymes were required to develop a coupled enzyme assay. None of the Mur enzymes or their substrates were available commercially, although purification procedures for the... 

UDP-MurNAc-L-Ala (UMA) and UDP-MurNAc-L-Ala-D-Glu (UMAE) were synthesized as described for the stem peptide [30], The synthesis of UMA was... 

The wild-type UDP-MurNAc-L-Ala-y-D-Glu-L-Lys-D-Ala-D-Ala (UDP-MurNAc-pentapeptide) was first isolated from S. aureus in 1952 by James Park [77], Nicolas Gisch et al. reported the synthesis of the biotinylated Lys-type and DAP-type muramyl tripeptides through their UDP derivatives [78], Both compounds activated Nod2 in a cell-based assay, although the required minimal motif for the activation of Nod2 is muramyl dipeptide [79], The chemical synthesis of the UDP-MurNAc-pentapeptide 7 (Scheme 14.1) [19] was followed by the chemoenzymatic synthesis by Chi-Huey Wong [80] and Michio Kurosu [81], Wong et al. also synthesized the vancomycin-resistant UDP-MurNAc-L-Ala-y-D-Glu-L-Lys-D-Ala-D-Lac... 

Early workers [29] found that, like benzylpenicillin, vancomycin, ristocetin and bacitracin, novobiocin caused an excessive accumulation of cell wall precursor, uridine diphosphate-7V-acetylmuramic acid-L-alanine-D-glutamic acid-L-lysine-D-alanine-D-alanine (UDP-MurNAc-L-ala-D-glu-L-lys-D-ala-D-ala) in Staph, aureus and it was thus considered that novobiocin was a specific inhibitor of peptidoglycan synthesis with an effect similar to that of penicillin. However, subsequent studies led to the withdrawal of this hypothesis [26], since novobiocin caused the accumulation of other precursor-type compounds and also strongly inhibited both nucleic acid and protein synthesis in this organism. Thus, accumulation of particular precursors does not necessarily reflect the site of action of an antibacterial agent [30]. 

Briefly, in E. colithe biosynthesis of PG initiates in cytosol with the formation of UDP-Macetylmuramic acid (UDP-MurNAc) from UDP-GlcNAc by a two-step reaction catalyzed by MurA and MurB. UDP-MurNAc is subsequently transformed into UOP-MurNAc-L-Ala-D-Glu-wcro-DAP-D-Ala-D-Ala (UDP-MurNAc-pentapeptide (UDP-MurNAc-PP) or Park s nucleotide) by sequential addition of L-Ala, d-G1u, wcro-DAP, and D-Ala-D-Ala catalyzed by MurC, D, E, and F, respectively. 

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