A Simple Procedure for Connecting Two Carbohydrate Moieties by Click Chemistry Techniques

Gouin, Sébastien G.; Bultel, Laurent; Falentin, Céline; Kovensky, José

doi:10.1002/ejoc.200600814

Cited by 36 publications

(11 citation statements)

References 52 publications

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“…28,31,32 In all cases, the reaction mixtures were followed by TLC and ESI-MS to evaluate the consumption of the starting materials. The latter technique was particularly useful to analyze reaction mixtures that involved polar partners of high molecular weight, difficult to detect by TLC.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…Coupling of 9 to the azide-containing scaffolds, 10 , 11 , and 16 , was conducted by click reaction in the presence of copper sulfate and sodium ascorbate in dioxane/H 2 O, under microwave irradiation (Scheme ). ,, In all cases, the reaction mixtures were followed by TLC and ESI-MS to evaluate the consumption of the starting materials. The latter technique was particularly useful to analyze reaction mixtures that involved polar partners of high molecular weight, difficult to detect by TLC.…”

Section: Resultsmentioning

confidence: 99%

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Design and Synthesis of Hydrolytically Stable Multivalent Ligands Bearing Thiodigalactoside Analogues for Peanut Lectin and Human Galectin-3 Binding

2014

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Herein, we describe the design and synthesis of a novel family of hydrolytically stable glycoclusters bearing thiodigalactoside (TDG) analogues as recognition elements of β-galactoside binding lectins. The TDG analogue was synthesized by thioglycosylation of a 6-S-acetyl-α-D-glucosyl bromide with the isothiouronium salt of 2,3,4,6-tetra-O-acetyl-β-D-galactose. Further propargylation of the TDG analogue allowed the coupling to azido-functionalized oligosaccharide scaffolds through copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) under microwave activation. The final mono-, di-, and tetravalent ligands were resistant to enzymatic hydrolisis by Escherichia coli β-galactosidase. Binding affinities to peanut agglutinin and human galectin-3 were measured by isothermal titration calorimetry which showed K(a) constants in the micromolar range as well as a multivalent effect. Monovalent ligand exhibited a binding affinity higher than that of thiodigalactoside. Docking studies performed with a model ligand on both β-galactoside binding lectins showed additional interactions between the triazole ring and lectin amino acid residues, suggesting a positive effect of this aromatic residue on the biological activity.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Design and Synthesis of Hydrolytically Stable Multivalent Ligands Bearing Thiodigalactoside Analogues for Peanut Lectin and Human Galectin-3 Binding

2014

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“…In order to increase the chemical diversity of our library of iminosugars, we have functionalized a set of commercial hydrophobic alcohols with propargyl bromide. The resulting compounds 31 – 34 and protected mannoside 35 were subsequently subjected to CuAAc with 4 or when the substituents were sensitive to the subsequent hydrogenolysis with 6 (Table ). As an illustrative example, attempts to selectively deprotect the benzyl groups of 36 led to the simultaneous removal of the two chlorine atoms in 75% yield.…”

Section: Resultsmentioning

confidence: 99%

Amphiphilic 1-Deoxynojirimycin Derivatives through Click Strategies for Chemical Chaperoning in N370S Gaucher Cells

et al. 2011

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In Gaucher disease (GD), mutant β-glucocerebrosidases (β-GCase) that are misfolded are recognized by the quality control machinery of the endoplasmic reticulum (ER) and degraded proteolytically. Hydrophobic iminosugars can be used as pharmacological chaperones to provide an improvement in the folding of the enzyme and promote trafficking from the ER. We have developed here an efficient click procedure to tether hydrophobic substituents to N-azidopropyl-1-deoxynojirimycin. A set of 14 original iminosugars was designed and evaluated for inhibition of commercially available glucosidases. Most of the compounds were micromolar inhibitors of those enzymes. In vitro inhibition assays with the N370S β-GCase revealed that the sublibrary containing the derivatives with aromatic aglycons displayed the highest inhibitory potency. Chaperone activity of the whole set of synthetic compounds was also explored in mutant Gaucher cells. The most active compound gave a nearly 2-fold increase in enzyme activity at 20 μM, a significantly higher value than the 1.33-fold recorded for the reference compound N-nonyl-1-deoxynojirimycin (N-nonyl-DNJ). As previously reported with bicyclic sp(2)-iminosugars (Luan, Z.; Higaki, K.; Aguilar-Moncayo, M.; Ninomiya, H.; Ohno, K.; García-Moreno, M. I.; Ortiz Mellet, C.; García Fernández, J. M.; Suzuki, Y. ChemBioChem 2009, 10, 2780), in vitro inhibition of β-GCase measured for the compounds did not correlate with the cellular chaperone activity. The potency of new iminosugar chaperones is therefore not predictable from structure-activity relationships studies based on the in vitro β-GCase inhibition.

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“…Besides making such divalent carbohydrates, sugars were also coupled to various amino acids. Other divalent sugars were prepared where the azido group on one of the coupling partners was placed at either the C-2, C-5 or the C-6 position [16], thus mimicking their position in complex natural oligosaccharides. As part of a study towards anticancer agents, a trivalent system was prepared consisting of a hexasaccharide in each of the linked arms to yield compound 13 [17].…”

Section: Multivalent Carbohydratesmentioning

confidence: 99%

Application of the 1,3‐Dipolar Cycloaddition Reaction in Chemical Biology: Approaches Toward Multivalent Carbohydrates and Peptides and Peptide‐Based Polymers

2007

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In this mini review we highlight our recent results and the related literature regarding the application of the Cu(I)-catalyzed 1,3-dipolar cycloaddition "click" reaction. The synthetic applications of the click reaction focus on multivalent carbohydrates and peptides and peptide-based polymers. Furthermore, a related reaction is described involving the coupling of thio acids and sulfonyl azides leading to the chemoselective formation of amides.

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A Simple Procedure for Connecting Two Carbohydrate Moieties by Click Chemistry Techniques

Abstract: We describe a procedure to link two saccharides by click chemistry techniques. This methodology allows the generation of new molecules in which two carbohydrates are connected through a triazole ring.

Cited by 36 publications

References 52 publications

Design and Synthesis of Hydrolytically Stable Multivalent Ligands Bearing Thiodigalactoside Analogues for Peanut Lectin and Human Galectin-3 Binding

Design and Synthesis of Hydrolytically Stable Multivalent Ligands Bearing Thiodigalactoside Analogues for Peanut Lectin and Human Galectin-3 Binding

Amphiphilic 1-Deoxynojirimycin Derivatives through Click Strategies for Chemical Chaperoning in N370S Gaucher Cells

Application of the 1,3‐Dipolar Cycloaddition Reaction in Chemical Biology: Approaches Toward Multivalent Carbohydrates and Peptides and Peptide‐Based Polymers

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