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David Goyard

Bio: David Goyard is an academic researcher from University of Grenoble. The author has contributed to research in topics: Medicine & Glycogen phosphorylase. The author has an hindex of 13, co-authored 31 publications receiving 525 citations. Previous affiliations of David Goyard include Claude Bernard University Lyon 1 & Université du Québec à Montréal.

Papers
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Journal ArticleDOI
TL;DR: This Review summarizes close to 500 primary publications and surveys published since 2000 about the syntheses and diverse bioactivities of C-glycopyranosyl (het)arenes displaying among others antioxidant, antiviral, antibiotic, antiadhesive, cytotoxic, and glycoenzyme inhibitory effects.
Abstract: This Review summarizes close to 500 primary publications and surveys published since 2000 about the syntheses and diverse bioactivities of C-glycopyranosyl (het)arenes. A classification of the preparative routes to these synthetic targets according to methodologies and compound categories is provided. Several of these compounds, regardless of their natural or synthetic origin, display antidiabetic properties due to enzyme inhibition (glycogen phosphorylase, protein tyrosine phosphatase 1B) or by inhibiting renal sodium-dependent glucose cotransporter 2 (SGLT2). The latter class of synthetic inhibitors, very recently approved as antihyperglycemic drugs, opens new perspectives in the pharmacological treatment of type 2 diabetes. Various compounds with the C-glycopyranosyl (het)arene motif were subjected to biological studies displaying among others antioxidant, antiviral, antibiotic, antiadhesive, cytotoxic, and glycoenzyme inhibitory effects.

151 citations

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TL;DR: PA-IL is a bacterial lectin from the opportunistic pathogen Pseudomonas aeruginosa and is involved in the recognition of glycoconjugates on human tissues and the glycoclusters obtained were evaluated as ligands of PA-IL and for their potential for competing with its binding to glycosylated surfaces.
Abstract: Multivalency is playing a major role in biological processes and particularly in lectin-carbohydrate interactions. The design of high-affinity ligands of lectins should provide molecules capable of interfering with these biological processes and potentially inhibit bacterial or viral infections. Azide-alkyne "click" chemistry was applied to the synthesis of dodecavalent fullerene-based glycoclusters. The conjugation could be efficiently performed from alkyne or azide functions on either partners (i.e. hexakis-fullerene adduct or glycoside). PA-IL is a bacterial lectin from the opportunistic pathogen Pseudomonas aeruginosa and is involved in the recognition of glycoconjugates on human tissues. The glycoclusters obtained were evaluated as ligands of PA-IL and for their potential for competing with its binding to glycosylated surfaces. The affinities measured by hemagglutination inhibition assay (HIA), enzyme-linked lectin assay (ELLA), and surface plasmon resonance (SPR) displayed a significant "glycoside cluster effect" with up to a 12,000-fold increase in binding when comparing a monovalent carbohydrate reference probe with a dodecavalent fullerene-based glycocluster, albeit with some differences depending on the analytical technique.

112 citations

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TL;DR: Twelve new d-glucopyranosylidene-spiro-isoxazolines have been prepared from O-peracylated exo-D- glucals by regio- and stereoselective 1,3-dipolar cycloaddition of nitrile oxides generated in situ by treatment of the corresponding oximes with bleach and these compounds decreased hepatic glucose production, which is known to be elevated in type 2 diabetes.

57 citations

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TL;DR: One of the first efficient and highly atropodiastereoselective approaches to glucose-based bis-triazoles as single atropisomers with aR stereochemistry is presented, which suggests that 4,5-disubstituted 1-glucosyl-1,2,3-Triazoles bind weakly to the enzyme.
Abstract: Whereas copper-catalyzed azide-alkyne cycloaddition (CuAAC) between acetylated β-D-glucosyl azide and alkyl or phenyl acetylenes led to the corresponding 4-substituted 1-glucosyl-1,2,3-triazoles in good yields, use of similar conditions but with 2 equiv CuI or CuBr led to the 5-halogeno analogues (>71 %). In contrast, with 2 equiv CuCl and either propargyl acetate or phenyl acetylene, the major products (>56 %) displayed two 5,5'-linked triazole rings resulting from homocoupling of the 1-glucosyl-4-substituted 1,2,3-triazoles. The 4-phenyl substituted compounds (acetylated, O-unprotected) and the acetylated 4-acetoxymethyl derivative existed in solution as a single form (d.r.>95:5), as shown by NMR spectroscopic analysis. The two 4-phenyl substituted structures were unambiguously identified for the first time by X-ray diffraction analysis, as atropisomers with aR stereochemistry. This represents one of the first efficient and highly atropodiastereoselective approaches to glucose-based bis-triazoles as single atropisomers. The products were purified by standard silica gel chromatography. Through Sonogashira or Suzuki cross-couplings, the 1-glucosyl-5-halogeno-1,2,3-triazoles were efficiently converted into a library of 1,2,3-triazoles of the 1-glucosyl-5-substituted (alkynyl, aryl) type. Attempts to achieve Heck coupling to methyl acrylate failed, but a stable palladium-associated triazole was isolated and analyzed by (1) H NMR and MS. O-Unprotected derivatives were tested as inhibitors of glycogen phosphorylase. The modest inhibition activities measured showed that 4,5-disubstituted 1-glucosyl-1,2,3-triazoles bind weakly to the enzyme. This suggests that such ligands do not fit the catalytic site or any other binding site of the enzyme.

32 citations

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TL;DR: Janus lectin this article is a chimeric bispecific lectin with two rationally oriented and distinct recognition surfaces, which is able to bind independently to both fucosylated and sialylated glycoconjugates.
Abstract: We engineered the first chimeric, bispecific lectin, with two rationally oriented and distinct recognition surfaces. This lectin, coined Janus lectin in allusion to the two-faced roman god, is able to bind independently to both fucosylated and sialylated glycoconjugates. The multivalent presentation of binding sites on each face of the Janus lectin is very efficient, resulting in avidities in the low nanomolar range for both fucosylated and sialylated surfaces. Moreover, novel heterovalent, bifunctional glycoclusters were synthetized that match the topology of the Janus lectin. Based on these tools, we constructed organized and controlled supramolecular architectures by assembling Janus lectin and glycocompound layer-by-layer. Furthermore, the Janus lectin was employed as biomolecular linker to organize protocells made from giant unilamellar vesicles of different nature, to more complex prototissues. In summary, tailor-made Janus lectins open wide possibilities for creating biomimetic matrices or artificial tissues.

27 citations


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705 citations

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TL;DR: This review highlights the successful advancement of Cu(I)-catalyzed click chemistry in glycoscience and its applications as well as future scope in different streams of applied sciences.
Abstract: Cu(I)-catalyzed azide–alkyne 1,3-dipolar cycloaddition (CuAAC), popularly known as the “click reaction”, serves as the most potent and highly dependable tool for facile construction of simple to complex architectures at the molecular level. Click-knitted threads of two exclusively different molecular entities have created some really interesting structures for more than 15 years with a broad spectrum of applicability, including in the fascinating fields of synthetic chemistry, medicinal science, biochemistry, pharmacology, material science, and catalysis. The unique properties of the carbohydrate moiety and the advantages of highly chemo- and regioselective click chemistry, such as mild reaction conditions, efficient performance with a wide range of solvents, and compatibility with different functionalities, together produce miraculous neoglycoconjugates and neoglycopolymers with various synthetic, biological, and pharmaceutical applications. In this review we highlight the successful advancement of Cu(I)...

557 citations

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TL;DR: By interfering with pathogen adhesion, such glycocompounds including glycopolymers, glycoclusters, glycodendrimers and glyconanoparticles have the potential to improve or replace antibiotic treatments that are now subverted by resistance.
Abstract: Multivalency plays a major role in biological processes and particularly in the relationship between pathogenic microorganisms and their host that involves protein-glycan recognition. These interactions occur during the first steps of infection, for specific recognition between host and bacteria, but also at different stages of the immune response. The search for high-affinity ligands for studying such interactions involves the combination of carbohydrate head groups with different scaffolds and linkers generating multivalent glycocompounds with controlled spatial and topology parameters. By interfering with pathogen adhesion, such glycocompounds including glycopolymers, glycoclusters, glycodendrimers and glyconanoparticles have the potential to improve or replace antibiotic treatments that are now subverted by resistance. Multivalent glycoconjugates have also been used for stimulating the innate and adaptive immune systems, for example with carbohydrate-based vaccines. Bacteria present on their surfaces natural multivalent glycoconjugates such as lipopolysaccharides and S-layers that can also be exploited or targeted in anti-infectious strategies.

449 citations

Journal ArticleDOI
TL;DR: An overview of the 1,2,3-triazole ring as a bioisostere for the design of drug analogs, highlighting relevant recent examples.

392 citations