An improved total synthesis of UDP-N-acetyl-muramic acid

Babič, Andréj; Pečar, Slavko

doi:10.1016/j.tetlet.2007.04.098

Cited by 13 publications

(10 citation statements)

References 20 publications

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“…This synthesis was improved and scaled up by Dini et al (2000). Recently, the synthesis was further modified and optimized using different protecting and coupling strategies (Babič & Pečar, 2007; Kurosu et al , 2007). The key steps of all these synthetic schemes are the introduction of the phosphate group at the anomeric centre of a suitably protected MurNAc derivative, and the coupling of MurNAc‐1‐phosphate with uridine 5′‐phosphomorpholidate.…”

Section: Biosynthesis Of the Udp‐murnac‐peptidesmentioning

confidence: 99%

Cytoplasmic steps of peptidoglycan biosynthesis

et al. 2008

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The biosynthesis of bacterial cell wall peptidoglycan is a complex process that involves enzyme reactions that take place in the cytoplasm (synthesis of the nucleotide precursors) and on the inner side (synthesis of lipid-linked intermediates) and outer side (polymerization reactions) of the cytoplasmic membrane. This review deals with the cytoplasmic steps of peptidoglycan biosynthesis, which can be divided into four sets of reactions that lead to the syntheses of (1) UDP-N-acetylglucosamine from fructose 6-phosphate, (2) UDP-N-acetylmuramic acid from UDP-N-acetylglucosamine, (3) UDP-N-acetylmuramyl-pentapeptide from UDP-N-acetylmuramic acid and (4) D-glutamic acid and dipeptide D-alanyl-D-alanine. Recent data concerning the different enzymes involved are presented. Moreover, special attention is given to (1) the chemical and enzymatic synthesis of the nucleotide precursor substrates that are not commercially available and (2) the search for specific inhibitors that could act as antibacterial compounds.

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Section: Biosynthesis Of the Udp‐murnac‐peptidesmentioning

confidence: 99%

Cytoplasmic steps of peptidoglycan biosynthesis

et al. 2008

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“…Two examples of synthetic procedures are described in Schemes 2 and 3 83–87 . To achieve diastereomerically pure MurNAc derivatives, D-Glucosamine and its equivalents are often used as starting materials.…”

Section: Synthetic Approach Of Mdp Analogsmentioning

confidence: 99%

Muramyl Dipeptide and its Derivatives: Peptide Adjuvant in Immunological Disorders and Cancer Therapy

Ogawa

Liu²,

Kobayashi³

2011

CBC

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Muramyl dipeptide (MDP) is a synthetic immunoreactive peptide consisting of N-acetyl muramic acid attached to a short amino acid chain of L-Ala-D-isoGln. It was first identified in bacterial cell wall peptidoglycan as an active component in Freund’s complete adjuvant. In the cell, MDP is detected by NOD2, a cytoplasmic receptor belonging to the human innate immune system. NOD2 mutations are frequently observed in patients with Crohn’s disease, an autoimmune disorder, suggesting the significance of the MDP-NOD2 pathway in activating immunity. For this reason, structural modifications of MDP and its derivatives have been extensively studied in an attempt to increase adjuvant activity and boost the immune response effectively for clinical use in the treatment of cancer and other diseases. This review summarizes the synthetic chemistry of MDP and its derivatives and discusses their pharmacological action and stereoselective synthesis.

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“…All NDP-X substrates were purchased from Sigma with the exception of UDP-N-acetylmuramic acid and UDP-N-acetylmuramoyl-L-Ala which were synthesized as described previously [6], [7]. The Nudix enzyme converts the CIP-insensitive Nudix substrates to CIP-reactive substrates, which release two molecules of orthophosphate upon reaction with CIP.…”

Section: Methodsmentioning

confidence: 99%

A UDP-X Diphosphatase from Streptococcus pneumoniae Hydrolyzes Precursors of Peptidoglycan Biosynthesis

Duong‐Ly¹,

Woo²,

Dunn³

et al. 2013

PLoS ONE

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The gene for a Nudix enzyme (SP_1669) was found to code for a UDP-X diphosphatase. The SP_1669 gene is localized among genes encoding proteins that participate in cell division in Streptococcus pneumoniae. One of these genes, MurF, encodes an enzyme that catalyzes the last step of the Mur pathway of peptidoglycan biosynthesis. Mur pathway substrates are all derived from UDP-glucosamine and all are potential Nudix substrates. We showed that UDP-X diphosphatase can hydrolyze the Mur pathway substrates UDP-N-acetylmuramic acid and UDP-N-acetylmuramoyl-L-alanine. The 1.39 Å resolution crystal structure of this enzyme shows that it folds as an asymmetric homodimer with two distinct active sites, each containing elements of the conserved Nudix box sequence. In addition to its Nudix catalytic activity, the enzyme has a 3′5′ RNA exonuclease activity. We propose that the structural asymmetry in UDP-X diphosphatase facilitates the recognition of these two distinct classes of substrates, Nudix substrates and RNA. UDP-X diphosphatase is a prototype of a new family of Nudix enzymes with unique structural characteristics: two monomers, each consisting of an N-terminal helix bundle domain and a C-terminal Nudix domain, form an asymmetric dimer with two distinct active sites. These enzymes function to hydrolyze bacterial cell wall precursors and degrade RNA.

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An improved total synthesis of UDP-N-acetyl-muramic acid

Cited by 13 publications

References 20 publications

Cytoplasmic steps of peptidoglycan biosynthesis

Cytoplasmic steps of peptidoglycan biosynthesis

Muramyl Dipeptide and its Derivatives: Peptide Adjuvant in Immunological Disorders and Cancer Therapy

A UDP-X Diphosphatase from Streptococcus pneumoniae Hydrolyzes Precursors of Peptidoglycan Biosynthesis

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