Synthesis of Fluorophore-Tagged Xylosides That Prime Glycosaminoglycan Chains

Tran, Vy M.; Kuberan, Balagurunathan

doi:10.1021/bc400396z

Cited by 12 publications

(18 citation statements)

References 25 publications

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“…21,32,33,35 For example, we have earlier investigated a series of hydroxynaphthyl 1-thio-β-D-xylopyranosides that all showed strong priming of relatively short GAG chains. 33,35,37 Kuberan and co-workers 27,28,34,[38][39][40] have made several series of amideand triazole-linked xylosides of which the GAG priming ability varied with variations in the aglycon moiety. 33,35,37 Kuberan and co-workers 27,28,34,[38][39][40] have made several series of amideand triazole-linked xylosides of which the GAG priming ability varied with variations in the aglycon moiety.…”

Section: Part B: Variation At the Anomeric Center Or Of Absolute Confmentioning

confidence: 99%

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Exploration of the active site of β4GalT7: modifications of the aglycon of aromatic xylosides

et al. 2015

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Proteoglycans (PGs) are macromolecules that consist of long linear polysaccharides, glycosaminoglycan (GAG) chains, covalently attached to a core protein by the carbohydrate xylose. The biosynthesis of GAG chains is initiated by xylosylation of the core protein followed by galactosylation by the galactosyltransferase β4GalT7. Some β-d-xylosides, such as 2-naphthyl β-d-xylopyranoside, can induce GAG synthesis by serving as acceptor substrates for β4GalT7 and by that also compete with the GAG synthesis on core proteins. Here we present structure-activity relationships for β4GalT7 and xylosides with modifications of the aromatic aglycon, using enzymatic assays, cell studies, and molecular docking simulations. The results show that the aglycons reside on the outside of the active site of the enzyme and that quite bulky aglycons are accepted. By separating the aromatic aglycon from the xylose moiety by linkers, a trend towards increased galactosylation with increased linker length is observed. The galactosylation is influenced by the identity and position of substituents in the aromatic framework, and generally, only xylosides with β-glycosidic linkages function as good substrates for β4GalT7. We also show that the galactosylation ability of a xyloside is increased by replacing the anomeric oxygen with sulfur, but decreased by replacing it with carbon. Finally, we propose that reaction kinetics of galactosylation by β4GalT7 is dependent on subtle differences in orientation of the xylose moiety.

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Section: Part B: Variation At the Anomeric Center Or Of Absolute Confmentioning

confidence: 99%

“…28 Recently, we made a systematic investigation of the effects of the xylose-aglycon distance on GAG priming ability. It has also been reported that a triazole-linker, compound 58, increased the GAG priming compared to 59.…”

Section: Part C: Variation Of Linker Lengthmentioning

confidence: 99%

Exploration of the active site of β4GalT7: modifications of the aglycon of aromatic xylosides

et al. 2015

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“…[61][62][84][85][86][87][88] Kuberan and co-workers have synthesized a large library of xylosides using click-chemistry, containing a triazole ring linked to the xylose residue. 69,72,[89][90] Naphthyl β-L-xylopyranoside does not prime GAG chains. 91 In order to study cellular effects, several Chinese hamster ovary (CHO) cell lines, with defect GAG biosynthesis have been developed: pgsA-745 cells lack the enzyme XylT2, pgsA-761 cells are defective in β4GalT7, and pgsI-208 cells are deficient in UXS1.…”

Section: Glycosaminoglycans and Proteoglycansmentioning

confidence: 99%

“…[61][62] Over the years, several hundred xylose derivatives have been synthesized and tested to explore cellular uptake, priming of GAG chains, and inhibition of biosynthetically important enzymes. Xylosides have been synthesized with variation in: the aglycon size and hydrophilicity, 57,[63][64][65][66][67][68][69][70] the distance between the carbohydrate and the aglycon, 63,69,[71][72] and the anomeric configuration. 57,[72][73][74][75][76][77][78] Furthermore, C-xylosides, 66,77,79 S-xylosides, 57, 63, 66, 76-77, 80 N-xylosides, 66 phosphorylated xylosides, 81 and peracylated xylosides [82][83] have been synthesized.…”

Section: Glycosaminoglycans and Proteoglycansmentioning

confidence: 99%

Chemistry of xylopyranosides

Thorsheim

Siegbahn

Johnsson

et al. 2015

Carbohydrate Research

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Xylose is one of the few monosaccharidic building blocks that are used by mammalian cells. In comparison with other monosaccharides, xylose is rather unusual and, so far, only found in two different mammalian structures, i.e. in the Notch receptor and as the linker between protein and glycosaminoglycan (GAG) chains in proteoglycans. Interestingly, simple soluble xylopyranosides can not only initiate the biosynthesis of soluble GAG chains but also function as inhibitors of important enzymes in the biosynthesis of proteoglycans. Furthermore, xylose is a major constituent of hemicellulosic xylans and thus one of the most abundant carbohydrates on Earth. Altogether, this has spurred a strong interest in xylose chemistry. The scope of this review is to describe synthesis of xylopyranosyl donors, as well as protective group chemistry, modifications, and conformational analysis of xylose.

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“…Western blots were conducted with monoclonal antibody CS56 (Sigma Aldrich) with goat antimouse IgM-HRP secondary (Fisher Scientific). Xylosides were synthesized, purified, and analyzed as previously described (Victor et al, 2009;Tsuzuki et al, 2010;Nguyen et al, 2013;Tran and Kuberan, 2014). All other reagents were acquired from Fisher Scientific or Sigma Aldrich.…”

Section: Reagentsmentioning

confidence: 99%

Regulation of glycosaminoglycan biogenesis is critical for sensitive‐period‐dependent vocal ontogeny

Tran

Quintero

Koketsu

et al. 2017

Developmental Neurobiology

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In the brain, the extracellular matrix (ECM) plays a central role during neural development and thus modulates critical-period regulated behavioral ontogeny. The major components of the ECM are glycosaminoglycans (GAGs) including chondroitin sulfate (CS). However, the specific roles of GAGs in behavioral development are largely unknown. It has been shown that xylosides affect the biological functions of GAGs through modulating GAG biosynthesis. Particularly, xylosides affect GAG biosynthesis through priming of GAG chains (priming activity), competing with endogenous core proteins that carry GAG initiation sites (decoy activity), or both. Using birdsong as our model, we investigated, for the first time, how xyloside-mediated modulation of GAG biogenesis affects song development. Xylosides infused into motor cortex of juvenile birds alter song development by specifically affecting ontogeny of the stereotyped sequence rather than the acoustic structure of syllables. Further analyses reveal that observed changes can be attributed to the priming activity rather than the decoy activity of xylosides. Collectively, these results suggest that regulation of GAG biogenesis through chemical biology approaches may allow promising therapeutic interventions of critical-period-dependent central nervous system plasticity. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1401-1412, 2017.

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Synthesis of Fluorophore-Tagged Xylosides That Prime Glycosaminoglycan Chains

Cited by 12 publications

References 25 publications

Exploration of the active site of β4GalT7: modifications of the aglycon of aromatic xylosides

Exploration of the active site of β4GalT7: modifications of the aglycon of aromatic xylosides

Chemistry of xylopyranosides

Regulation of glycosaminoglycan biogenesis is critical for sensitive‐period‐dependent vocal ontogeny

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