Synthesis of a tetrasaccharide substrate of heparanase

Chen, Jianfang; Zhou, Ying; Chen, Chen; Xü, Wei; Yu, Biao

doi:10.1016/j.carres.2008.06.011

Cited by 38 publications

(18 citation statements)

References 42 publications

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“…Compounds 1 – 3 were synthesized using a divergent strategy, starting from the common intermediate 4 , [24] obtained from commercial D-glucosamine hydrochloride (Scheme 2). Compound 4 has been treated with PPh 3 in THF/H 2 O to transform the azido group into amine (compound 5 ), then acylated in C-2 and C-3 positions using myristic acid in the presence of the condensing agent 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), thus affording 6 .…”

Section: Resultsmentioning

confidence: 99%

Modulation of CD14 and TLR4⋅MD‐2 Activities by a Synthetic Lipid A Mimetic

et al. 2013

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Monosaccharide lipid A mimetics composed by a glucosamine core linked to two fatty acid chains and bearing one or two phosphates have been synthesized. While compounds 1 and 2, with one phosphate group, were practically inactive in inhibiting LPS-induced TLR4 signaling and cytokine production in HEK-blue™ cells and murine macrophages, compound 3 with two phosphates was found to be active in efficiently inhibiting TLR4 signal in both cell types. The direct interaction of molecule 3 with MD-2 co-receptor has been investigated by means of NMR and molecular modeling/docking analysis. This compound also interacts directly with CD14 receptor, stimulating its internalization by endocytosis. Experiments on macrophages show that the effect on CD14 reinforces the activity on MD-2.TLR4, because compound 3 activity is higher when CD14 is important for TLR4 signaling i,e, at low LPS concentration. The dual MD-2 and CD14 targeting, accompanied by good solubility in water and lack of toxicity, suggests the use of monosaccharide 3 as a lead compound to develop drugs directed against TLR4-related syndromes.

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Section: Resultsmentioning

confidence: 99%

Modulation of CD14 and TLR4⋅MD‐2 Activities by a Synthetic Lipid A Mimetic

et al. 2013

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“…However, 2 is only accessible via laborious total synthesis [ 58 ], whereas 1 is commercially available. Simpler HS tri- or tetrasaccharides have been synthesised as putative heparanase substrates (e.g., Figure 3 ) [ 59 , 60 , 61 ]. The degradation of these substrates by heparanase should be amenable to detection by similar means as described for 1 , e.g., via WST-1 or resazurin, but to date this has not been reported.…”

Section: Assaying Heparanasementioning

confidence: 99%

The Development of Assays for Heparanase Enzymatic Activity: Towards a Gold Standard

Chhabra

Ferro

2018

Molecules

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The enzyme heparanase, an endo-β-glucuronidase, degrades heparan sulfate (HS) chains on the cell surface and in the extracellular matrix. Heparanase regulates numerous biological processes that drive tumour growth, metastasis and angiogenesis. In addition to its key role in cancer progression, it has also been implicated in an ever-growing number of other diseases, particularly those associated with inflammation. The importance of heparanase in biology has led to numerous efforts over the years to develop assays to monitor its activity and to screen for new inhibitors as potential drug candidates. Despite these efforts and the commercialization of a few kits, most heparanase assays are still complex, labour intensive, costly or have limited application. Herein we review the various methods for assaying heparanase enzymatic activity, focusing on recent developments towards new assays that hold the promise of accelerating research into this important enzyme.

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“…37,59,60 The Boons group used this strategy to prepare disaccharide building blocks for their heparin/HS oligosaccharide synthesis (Scheme 20). 59 Glycosylation of 1-thioglycoside donor 120 with the TDS-protected acceptor 121 formed the latent disaccharide 122 .…”

Section: Active–latent Glycosylation Strategymentioning

confidence: 99%

“…Adjustment of the oxidation state can then be performed on the disaccharide through oxidation at C-6 of the nonreducing end to the uronic acid, thus avoiding a late-stage oxidation of the more-valuable larger oligosaccharides (Scheme 4D). 59,60 …”

Section: Introductionmentioning

confidence: 99%