Total synthesis of uridine diphosphate-N-acetylmuramoyl-l-alanine

Babič, Andréj; Pečar, Slavko

doi:10.1016/j.tetasy.2008.09.029

Cited by 12 publications

(12 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The present work marks the first reliable preparation of this dipeptide structural type with complete spectroscopic characterization of all intermediates and final products (see Supporting Information for details). In addition, the synthesis of carbohydrate fragments produced N -acetyl glucosamine scaffolds as single α-anomers. , Retrosynthetically, analogues 6 and 3 could be derived respectively through removal of the ketal of 4 and 5 (Scheme ). Analogues 4 and 5 could be constructed by standard peptide coupling between carboxylic acids 7a and 7b and dipeptide 8 , which were synthesized respectively from commercially available N -acetyl- d -glucosamine and d -glutamic acid.…”

Section: Resultsmentioning

confidence: 99%

Convergent Synthesis of Novel Muramyl Dipeptide Analogues: Inhibition of Porphyromonas gingivalis-Induced Pro-inflammatory Effects by High Doses of Muramyl Dipeptide

2016

View full text Add to dashboard Cite

Porphyromonas gingivalis (P.g.)-induced TNF-α can be affected by muramyl dipeptide (MDP) in a biphasic concentration-dependent manner. We found that in P.g.-exposed macrophages, treatment with 10 μg/mL of MDP (MDP-low) up-regulated TNF-α by 29%, while 100 μg/mL or higher (MDP-high) significantly decreased it (16% to 38%). MDP-high was found to affect the ubiquitin-editing enzyme A20 and activator protein 1 (AP1). An AP1 binding site was found in the promoter region of A20. A20 promoter activity was up-regulated after transfection of AP1 cDNA in cells. Four analogues of MDP (3-6) were prepared through a convergent strategy involving the synthesis of two unique carbohydrate fragments, 7a and 7b, using the peptide coupling reagents, EDCI and HOAt. Analogue 4 improved MDP function and P.g.-induced activities. We propose a new signaling pathway for TNF-α induction activated after exposing macrophages to both P.g. and MDP-high or analogue 4.

show abstract

Section: Resultsmentioning

confidence: 99%

Convergent Synthesis of Novel Muramyl Dipeptide Analogues: Inhibition of Porphyromonas gingivalis-Induced Pro-inflammatory Effects by High Doses of Muramyl Dipeptide

2016

View full text Add to dashboard Cite

show abstract

“…[25][26][27][28][29] The synthesis started from N-acetylglucosamine 1, which was protected by benzylation with benzyl alcohol at the anomeric position. 19 The p-toluene sulfonic acid was used as a catalyst in the reaction which was carried out in toluene.…”

Section: Resultsmentioning

confidence: 99%

“…The synthesis resulted in a α/ β mixture of benzyl anomer 2, however the pure benzyl α-anomer 2 can be obtained with thermodynamic control of the reaction by high temperature in refluxing toluene. 29 The incorporation of a benzylidene protection group in the 4-O and 6-O-hydroxy positions was carried out according to previously published Gross and Jeanloz strategy to afford protected N-acetylglucosamine derivative 3 with a free 3-hydroxy group. 21 The method for the efficient and easy synthesis of 4,6-benzylidne-derivative of N-acetylglucosamine, using pyridinium perchlorate as catalyst in the reaction with benzaldehyde dimethylacetal, was recently published.…”

Section: Resultsmentioning

confidence: 99%

“…The benzylidene proton at 5.68 ppm for the muramic acid derivative 4 is indicative of the muramic acid derivative with the (R)-configuration of the lactyl sidechain according to the published data by Babič and Pečar which are for the muramic acid 5.66 ppm and for the isomuramic acid 5.55 ppm. 29 The determination of the absolute configuration was especially important in the next step in the reaction of saponification of the compound 4, to deprotect amino group and give compound 5. This reaction conditions enable racemisation.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Synthesis of Orthogonally Protected Muramic Acid Building Blocks for Solid Phase Peptide Synthesis

Vlahoviček-Kahlina¹,

Jakas²

2015

Croat. Chem. Acta

View full text Add to dashboard Cite

show abstract

“…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

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Total synthesis of uridine diphosphate-N-acetylmuramoyl-l-alanine

Cited by 12 publications

References 27 publications

Convergent Synthesis of Novel Muramyl Dipeptide Analogues: Inhibition of Porphyromonas gingivalis-Induced Pro-inflammatory Effects by High Doses of Muramyl Dipeptide

Convergent Synthesis of Novel Muramyl Dipeptide Analogues: Inhibition of Porphyromonas gingivalis-Induced Pro-inflammatory Effects by High Doses of Muramyl Dipeptide

Synthesis of Orthogonally Protected Muramic Acid Building Blocks for Solid Phase Peptide Synthesis

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

Contact Info

Product

Resources

About