- Rational Design of Glycomimetic Compounds Targeting the Saccharomyces cerevisiae Transglycosylase Gas2
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The transglycosylase Saccharomyces cerevisiae Gas2 (ScGas2) belongs to a large family of enzymes that are key players in yeast cell wall remodeling. Despite its biologic importance, no studies on the synthesis of substrate-based compounds as potential inhibitors have been reported. We have synthesized a series of docking-guided glycomimetics that were evaluated by fluorescence spectroscopy and saturation-transfer difference (STD) NMR experiments, revealing that a minimum of three glucose units linked via a β-(1,3) linkage are required for achieving molecular recognition at the binding donor site. The binding mode of our compounds is further supported by STD-NMR experiments using the active site-mutants Y107Q and Y244Q. Our results are important for both understanding of ScGas2-substrate interactions and setting up the basis for future design of glycomimetics as new antifungal agents.
- Delso, Ignacio,Valero-González, Jessika,Marca, Eduardo,Tejero, Tomás,Hurtado-Guerrero, Ramón,Merino, Pedro
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- Oligo-β-(1 → 3)-glucans: Impact of thio-bridges on immunostimulating activities and the development of cancer stem cells
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Recent developments of innovative anticancer therapies are based on compounds likely to stimulate the immune defense of the patients. β-(1 → 3)-Glucans are natural polysaccharides well-known for their immunostimulating properties. We report here on the synthesis of small oligo-β-(1 → 3)-glucans characterized by thioglycosidic linkages. The presence of sulfur atom(s) was not only crucial to prolong in vivo immunoactive activities in time, compared to native polysaccharides, but sulfur atoms also had a direct impact on the development of colorectal cancer stem cells. As a result, a short, pure, and structurally well-defined trisaccharidic thioglucan demonstrated similar activities compared to those of natural laminarin.
- Sylla, Balla,Legentil, Laurent,Saraswat-Ohri, Sujata,Vashishta, Aruna,Daniellou, Richard,Wang, Hsei-Wei,Vetvicka, Vaclav,Ferrières, Vincent
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- Orthogonal Active-Site Labels for Mixed-Linkage endo-β-Glucanases
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Small molecule irreversible inhibitors are valuable tools for determining catalytically important active-site residues and revealing key details of the specificity, structure, and function of glycoside hydrolases (GHs). β-glucans that contain backbone β(1,3) linkages are widespread in nature, e.g., mixed-linkage β(1,3)/β(1,4)-glucans in the cell walls of higher plants and β(1,3)glucans in yeasts and algae. Commensurate with this ubiquity, a large diversity of mixed-linkage endoglucanases (MLGases, EC 3.2.1.73) and endo-β(1,3)-glucanases (laminarinases, EC 3.2.1.39 and EC 3.2.1.6) have evolved to specifically hydrolyze these polysaccharides, respectively, in environmental niches including the human gut. To facilitate biochemical and structural analysis of these GHs, with a focus on MLGases, we present here the facile chemo-enzymatic synthesis of a library of active-site-directed enzyme inhibitors based on mixed-linkage oligosaccharide scaffolds and N-bromoacetylglycosylamine or 2-fluoro-2-deoxyglycoside warheads. The effectiveness and irreversibility of these inhibitors were tested with exemplar MLGases and an endo-β(1,3)-glucanase. Notably, determination of inhibitor-bound crystal structures of a human-gut microbial MLGase from Glycoside Hydrolase Family 16 revealed.
- Jain, Namrata,Tamura, Kazune,Déjean, Guillaume,Van Petegem, Filip,Brumer, Harry
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p. 1968 - 1984
(2021/05/26)
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- NATURAL AND SYNTHETIC DITERPENE GLYCOSIDES, COMPOSITIONS AND METHODS
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Novel diterpene glycosides isolated from Stevia extract as well as diterpene glycosides that are synthetically prepared are provided herein. Compositions and consumables comprising the novel diterpene glycosides are also provided herein. Methods of enhancing the sweetness and/or flavor of consumables using the novel diterpene glycosides, methods of preparing compositions and consumables comprising the novel diterpene glycosides, methods of purifying the novel diterpene glycosides and methods of synthesizing the diterpene glycosides are also provided.
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Page/Page column 99; 103-104
(2019/08/12)
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- Stereoselective Ethynylation and Propargylation of Chiral Cyclic Nitrones: Application to the Synthesis of Glycomimetics
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Ethynylation and propargylation of chiral nonracemic polyhydroxylated cyclic nitrones with Grignard reagents are efficient methods for preparing building blocks containing an alkyne moiety to be used in copper-catalyzed azide alkyne cycloaddition click chemistry. Whereas ethynylation takes place with excellent diastereoselectivity, propargylation afforded mixtures of diastereomers in some cases. The use of (trimethylsilyl)propargyl bromide as precursor of the Grignard reagent is necessary to avoid the formation of undesired allene derivatives. DFT calculations explain, within the experimental error, the observed behavior. Cycloaddition of the obtained pyrrolidinyl alkynes with sugar azides derived from β-(1,3)-glucans provides glycomimetics suitable to be used against fungal transglycosylases.
- García-Vi?uales, Sara,Delso, Ignacio,Merino, Pedro,Tejero, Tomás
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p. 3339 - 3351
(2016/09/09)
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- Synthesis of O- and C-glycosides derived from β-(1,3)-d-glucans
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A series of β-(1,3)-d-glucans have been synthesized incorporating structural variations specifically on the reducing end of the oligomers. Both O- and C-glucosides derived from di- and trisaccharides have been obtained in good overall yields and with comp
- Marca, Eduardo,Valero-Gonzalez, Jessika,Delso, Ignacio,Tejero, Tomás,Hurtado-Guerrero, Ramon,Merino, Pedro
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- Transglycosylation activity of Bacillus 1,3-1,4-β-D-glucan 4-glucanohydrolases. Enzymic synthesis of alternate 1,3,-1,4-β-D-glucooligosaccharides
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The title enzyme from Bacillus licheniformis has been shown to catalyse the effective autocondensation of β-laminaribiosyl fluoride, and lead to alternate 1,3-1,4-β-D-glucotetraose and -glucohexaose products. The transglycosylation using the same donor an
- Viladot, Josep-Lluis,Moreau, Vincent,Planas, Antoni,Driguez, Hugues
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p. 2383 - 2387
(2007/10/03)
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- Peracetylated laminaribiose: Preparation by specific degradation of curdlan and its chemical conversion into N-acetylhyalobiuronic acid
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β-Laminaribiose octaacetate (2b) was prepared in greater than 50% yield from the microbial polysaccharide curdlan by specific degradation with a yeast cell-wall lytic enzyme preparation, Kitalase, and subsequent acetylation. Acetolysis of curdlan also gav
- Wang,Sakairi,Kuzuhara
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p. 133 - 148
(2007/10/02)
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- Synthese und 1H-NMR-Studie der vier unverzweigten peracetylierten β-D-Glucopyranosyl-β-gentiobiosen
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With regard to the structure elucidation of an unknown trisaccharide isolated from the stigmas of garden crocusses (Crocus neapolitanus var.), the four unbranched (1->6)-, (1->4)-, (1->3)-, and (1->2)-connected β-D-glucopyranosyl-β-gentiobiose peracetates were synthesized.A complete analysis of the 1H-NMR spectra of the four trisaccharide peracetates was carried out.
- Rychener, Martin,Bigler, Peter,Pfander, Hanspeter
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p. 378 - 385
(2007/10/02)
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- SYNTHESIS OF A BRANCHED D-GLUCOTETRAOSE, THE REPEATING UNIT OF THE EXTRACELLULAR POLYSACCHARIDES OF Grifola umbellate, Sclerotinia libertiana, Porodisculus pendulus, AND Schizophyllum commune FRIES
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The synthesis of D-glucotetraose, 3-O--6-O-β-D-glucopyranosyl-α (and β)-D-glucopyranose, the repeating unit of the extracellular polysaccharides of Grifora umbellata, Sclerotinia libertiana, Porodisculus pendulus, and Schizophyllum commune Fries, is described.
- Ogawa, Tomoya,Kaburagi, Toshiaki
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