4-Deoxy-4-fluoro-xyloside derivatives as inhibitors of glycosaminoglycan biosynthesis

Tsuzuki, Yasuhiro; Nguyen, Thao Kim Nu; Garud, Dinesh R.; Kuberan, Balagurunathan; Koketsu, Mamoru

doi:10.1016/j.bmcl.2010.10.085

Cited by 34 publications

(28 citation statements)

References 19 publications

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“…[22] As shown in Figure 1, only xylosides III and IV were able to inhibit tube formation at 300 μM concentration. No other fluoro-xylosides tested had any effect on tube formation at this concentration.…”

Section: Resultsmentioning

confidence: 99%

“…There is a direct correlation between the most potent inhibitors of tube formation and the most potent inhibitors of GAG synthesis. [22] Since we have previously shown that cell surface heparan sulfates are essential players in the process of tube formation, it is likely that these fluoro-xylosides prevent tube formation by inhibiting GAG production. [21] Not only are these fluoro-xylosides ideal drug candidates due to their small size and their ability to penetrate cells, they are also excellent chemical biology tools to probe proteoglycan biology.…”

Section: Resultsmentioning

confidence: 99%

“…[21] Recently, we found that several novel fluoro-xylosides selectively inhibited GAG synthesis in vitro in endothelial cells (Table 1). [22] Based on these results, we hypothesized that these fluoro-xylosides would be effective inhibitors of endothelial tube formation as well. In this article we utilize the matrigel tube formation assay to show the anti-angiogenic efficacy of these novel fluoro-xylosides.…”

Section: Introductionmentioning

confidence: 99%

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Novel glycosaminoglycan biosynthetic inhibitors affect tumor-associated angiogenesis

Raman

Ninomiya

Nguyen

et al. 2011

Biochemical and Biophysical Research Communications

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Heparan sulfate proteoglycans (HSPGs) are essential players in several steps of tumor-associated angiogenesis. As co-receptors for several pro-angiogenic factors such as VEGF and FGF, HSPGs regulate receptor-ligand interactions and play a vital role in signal transduction. Previously, we have employed an enzymatic strategy to show the importance of cell surface HSPGs in endothelial tube formation in vitro. We have recently found several fluoro-xylosides that can selectively inhibit proteoglycan synthesis in endothelial cells. The current study demonstrates that these fluoro-xylosides are effective inhibitors of endothelial tube formation in vitro using a matrigel based assay to simulate tumor-associated angiogenesis. These first generation scaffolds offer a promising stepping-stone to the discovery of more potent fluoro-xylosides that can effectively neutralize tumor growth.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Novel glycosaminoglycan biosynthetic inhibitors affect tumor-associated angiogenesis

Raman

Ninomiya

Nguyen

et al. 2011

Biochemical and Biophysical Research Communications

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“…[151] Among these derivatives some derivatives were found to be very good inhibitors of glycosaminoglycan biosynthesis.…”

Section: Antifungal and Antibacterialsmentioning

confidence: 99%

Click Chemistry: 1,2,3‐Triazoles as Pharmacophores

Agalave

Maujan

Pore

2011

Chemistry An Asian Journal

1,149

508

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The copper(I)-catalyzed 1,2,3-triazole-forming reaction between azides and terminal alkynes has become the gold standard of click chemistry due to its reliability, specificity, and biocompatibility. Applications of click chemistry are increasingly found in all aspects of drug discovery; they range from lead finding through combinatorial chemistry and target-templated in vitro chemistry, to proteomics and DNA research by using bioconjugation reactions. The triazole products are more than just passive linkers; they readily associate with biological targets, through hydrogen-bonding and dipole interactions. The present review will focus mainly on the recent literature for applications of this reaction in the field of medicinal chemistry, in particular on use of the 1,2,3-triazole moiety as pharmacophore.

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“…This was investigated using xyloside 3 , a xyloside that has been shown to inhibit naturally occurring protein‐bound GAG production but lacks the priming aspect of the other xylosides 1 and 2 used in this study (Tsuzuki et al, ). As predicted, treatment with inhibitory xyloside 3 showed no change in the development of stereotyped syllable sequence, following a similar trajectory as that of control birds.…”

Section: Discussionmentioning

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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4-Deoxy-4-fluoro-xyloside derivatives as inhibitors of glycosaminoglycan biosynthesis

Cited by 34 publications

References 19 publications

Novel glycosaminoglycan biosynthetic inhibitors affect tumor-associated angiogenesis

Novel glycosaminoglycan biosynthetic inhibitors affect tumor-associated angiogenesis

Click Chemistry: 1,2,3‐Triazoles as Pharmacophores

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

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