Toward Analogues of MraY Natural Inhibitors: Synthesis of 5′-Triazole-Substituted-Aminoribosyl Uridines Through a Cu-Catalyzed Azide–Alkyne Cycloaddition

Fer, Mickaël J; Olatunji, Samir; Bouhss, Ahmed; Calvet-Vitale, Sandrine; Gravier‐Pelletier, Christine

doi:10.1021/jo4014035

Cited by 22 publications

(23 citation statements)

References 73 publications

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“…Recently,t he importance of MraY in bacterial peptidoglycansynthesis has prompted major interesti nt he development of simplified nucleoside antibiotic analogues in the search for novel antimicrobial strategies. [7][8][9][10][11] PGTsa lso feature in eukaryoticb iology,m ost prominently at the initiation of the dolichol-dependent glycosylationp athway, where aG lcNAc-1-phosphate transferase (GPT),d esignated as Alg7 in Saccharomyces cerevisiae and other eukaryotes, transfers phospho-GlcNAc to dolichol phosphate. [12] Sequence analysis of WecA and Alg7 reveals that these enzymes are both integralm embrane proteins with 11 predicted transmembrane helices (TMHs) and that they share key predicted active site residues,t herefore it is unsurprising that Alg7 is also potently inhibited by tunicamycin [13] (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

A Modular Approach to Phosphoglycosyltransferase Inhibitors Inspired by Nucleoside Antibiotics

Walvoort

Lukose

Imperiali

2015

Chemistry A European J

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Phosphoglycosyl transferases (PGTs) represent “gatekeeper” enzymes in complex glycan assembly pathways by catalyzing transfer of a phosphosugar from an activated nucleotide diphosphosugar to a membrane-resident polyprenol phosphate. The unique structures of selected nucleoside antibiotics, such as tunicamycin and mureidomycin A, which are known to inhibit comparable biochemical transformations, are exploited as the foundation for the development of modular synthetic inhibitors of PGTs. Herein we present the design, synthesis, and biochemical evaluation of two readily manipulatable modular scaffolds as inhibitors of monotopic bacterial PGTs. Selected compounds show IC50 values down to the 40 μm range, thereby serving as lead compounds for future development of selective and effective inhibitors of diverse PGTs of biological and medicinal interest.

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Section: Introductionmentioning

confidence: 99%

A Modular Approach to Phosphoglycosyltransferase Inhibitors Inspired by Nucleoside Antibiotics

Walvoort

Lukose

Imperiali

2015

Chemistry A European J

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“…Structural modification of known inhibitors provides a useful approach in developing novel inhibitors. An interesting example of this is the synthesis of 5′-triazole-substituted-aminoribosyl uridines (liposidomycin, caprazamycin or muraymycin) through Cu-catalyzed azide-alkyne cycloaddition (click chemistry) [ 72 ]. The 14 molecules investigated in this study exhibited IC 50 values typically between 50 and 100 µM.…”

Section: Mraymentioning

confidence: 99%

The Membrane Steps of Bacterial Cell Wall Synthesis as Antibiotic Targets

Liu

Breukink

2016

Antibiotics

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Peptidoglycan is the major component of the cell envelope of virtually all bacteria. It has structural roles and acts as a selective sieve for molecules from the outer environment. Peptidoglycan synthesis is therefore one of the most important biogenesis pathways in bacteria and has been studied extensively over the last twenty years. The pathway starts in the cytoplasm, continues in the cytoplasmic membrane and finishes in the periplasmic space, where the precursor is polymerized into the peptidoglycan layer. A number of proteins involved in this pathway, such as the Mur enzymes and the penicillin binding proteins (PBPs), have been studied and regarded as good targets for antibiotics. The present review focuses on the membrane steps of peptidoglycan synthesis that involve two enzymes, MraY and MurG, the inhibitors of these enzymes and the inhibition mechanisms. We also discuss the challenges of targeting these two cytoplasmic membrane (associated) proteins in bacterial cells and the perspectives on how to overcome the issues.

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“…Interestingly, the same methodology was proved to be suitable with hexopyranose skeletons to construct 1,6‐anhydro hexopyranose. Direct Mitsunobu reaction on 2,3‐ O ‐isopropylidene‐ d ‐ribose was attempted to provide 1,5‐anhydro‐2,3‐ O ‐isopentylidene‐ d ‐ribofuranose in moderate yield, indicating the potential application of the Mitsunobu reaction to such intramolecular etherification . In 2009, Fraser‐Reid and co‐workers developed a reaction of 1,2‐orthoesters ( 211 ) with HF/pyridine to prepare glycosyl fluorides .…”

Section: 4‐anhydro Pyranose/15‐anhydro Furanose (27‐dioxabicyclomentioning

confidence: 99%

The Construction of Anhydro Monosaccharides

Xie

Lin

et al. 2016

Asian J Org Chem

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Anhydro monosaccharide is as pecific and distinctive category of carbohydrates, which is found in many naturally deriveda nd artificial bioactive substrates. In the field of organic chemistry,s ome anhydro sugars can be used as common synthons to construct different carbohydrate structures. The development of efficient methodologies for the constructiono fv ariousa nhydro sugar fragments is very important in carbohydrate chemistry,w hich has attracted considerable attention in the past few years. This reviewm ainly covers the development of new synthetic methods since 2000 and gives an overview of the development in the formation of anhydro monosaccharide structures. It systematically summarizes all methodst oe stablish an intramolecular ether bridge in furanose and pyranose structures, which are the mostc ommonly used monosaccharide fragments in carbohydrate chemistry.

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Toward Analogues of MraY Natural Inhibitors: Synthesis of 5′-Triazole-Substituted-Aminoribosyl Uridines Through a Cu-Catalyzed Azide–Alkyne Cycloaddition

Cited by 22 publications

References 73 publications

A Modular Approach to Phosphoglycosyltransferase Inhibitors Inspired by Nucleoside Antibiotics

A Modular Approach to Phosphoglycosyltransferase Inhibitors Inspired by Nucleoside Antibiotics

The Membrane Steps of Bacterial Cell Wall Synthesis as Antibiotic Targets

The Construction of Anhydro Monosaccharides

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