Uronic Acids in Oligosaccharide Synthesis

Bos, Leendert J. van den; Codée, Jeroen D. C.; Litjens, Remy E. J. N.; Dinkelaar, Jasper; Overkleeft, Herman S.; Marel, Gijsbert A. van der

doi:10.1002/ejoc.200700101

Cited by 75 publications

(40 citation statements)

References 149 publications

(77 reference statements)

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“…The modest yield was attributed to the presence of the protected aminopentyl linker, which in our experience lowers yields of glycosylations. Furthermore, uronic acids are notoriously poor glycosyl acceptors, 25 which is attenuated by the electron-withdrawing groups at C-2 and C-6 of acceptor 11 . The process of Fmoc removal and glycosylation was repeated twice by employing glycosyl donors 8 and 9 to give fully protected octasaccharide 16 .…”

Section: Resultsmentioning

confidence: 99%

Integrated Approach to Identify Heparan Sulfate Ligand Requirements of Robo1

Zong¹,

Huang²,

Condac³

et al. 2016

J. Am. Chem. Soc.

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An integrated methodology is described to establish ligand requirements for heparan sulfate (HS) binding proteins based on a workflow in which HS octasaccharides are produced by partial enzymatic degradation of natural HS followed by size exclusion purification, affinity enrichment using an immobilized HS-binding protein of interest, putative structure determination of isolated compounds by a hydrophilic interaction chromatography–high-resolution mass spectrometry platform, and chemical synthesis of well-defined HS oligosaccharides for structure–activity relationship studies. The methodology was used to establish the ligand requirements of human Roundabout receptor 1 (Robo1), which is involved in a number of developmental processes. Mass spectrometric analysis of the starting octasaccharide mixture and the Robo1-bound fraction indicated that Robo1 has a preference for a specific set of structures. Further analysis was performed by sequential permethylation, desulfation, and pertrideuteroacetylation followed by online separation and structural analysis by MS/MS. Sequences of tetrasaccharides could be deduced from the data, and by combining the compositional and sequence data, a putative octasaccharide ligand could be proposed (GlA-GlcNS6S-IdoA-GlcNS-IdoA2S-GlcNS6S-IdoA-GlcNAc6S). A modular synthetic approach was employed to prepare the target compound, and binding studies by surface plasmon resonance (SPR) confirmed it to be a high affinity ligand for Robo1. Further studies with a number of tetrasaccharides confirmed that sulfate esters at C-6 are critical for binding, whereas such functionalities at C-2 substantially reduce binding. High affinity ligands were able to reverse a reduction in endothelial cell migration induced by Slit2-Robo1 signaling.

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Section: Resultsmentioning

confidence: 99%

Integrated Approach to Identify Heparan Sulfate Ligand Requirements of Robo1

Zong¹,

Huang²,

Condac³

et al. 2016

J. Am. Chem. Soc.

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“…However, due to the presence of the electron withdrawing carboxylic acid, glucuronic acid thioglycoside derivatives have been rarely used as glycosyl donors 28–31. Instead, thioglucosides are typically employed, which require oxidation state adjustment after the glycosylation 28,32. It will be desirable to be able to use protected glucuronic acid derivatives directly as glycosyl donors.…”

Section: Resultsmentioning

confidence: 99%

Installation of Electron-Donating Protective Groups, a Strategy for Glycosylating Unreactive Thioglycosyl Acceptors using the Preactivation-Based Glycosylation Method

et al. 2008

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The pre-activation based chemoselective glycosylation is a powerful strategy for oligosaccharide synthesis with its successful application in assemblies of many complex oligosaccharides. However, difficulties were encountered in reactions where glycosyl donors bearing multiple electron withdrawing groups failed to glycosylate hindered unreactive acceptors. In order to overcome this problem, it was discovered that the introduction of electron donating protective groups onto the glycosyl donors can considerably enhance their glycosylating power, leading to productive glycosylations even with unreactive acceptors. This observation is quite general, which can be extended to a wide range of glycosylation reactions, including one-pot syntheses of chondroitin and heparin trisaccharides. The structures of the reactive intermediates formed upon pre-activation were determined through low temperature NMR studies. It was found that for a donor with multiple electron withdrawing groups, the glycosyl triflate was formed following pre-activation, while the dioxalenium ion was the major intermediate with a donor bearing electron donating protective groups. As donors were all cleanly pre-activated prior to the addition of the acceptors, the observed reactivity difference between these donors was not due to selective activation encountered in the traditional armed-disarmed strategy. Rather, it was rationalized by the inherent internal energy difference between the reactive intermediates and associated oxacarbenium ion like transition states during nucleophilic attack by the acceptor.

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“…[39][40][41][42][43][44][45] Further, aldehydes generated by partial oxidation of polysaccharides can undergo Schiff-base formation with primary amines [43,46] (e.g., lysine residues) for the covalent attachment of proteins. [47,48] In initial studies, we identified conditions to electrodeposit and activate chitosan films for protein assembly.…”

mentioning

confidence: 99%

Reagentless Protein Assembly Triggered by Localized Electrical Signals

et al. 2009

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There is great interest in coupling the capabilities of electronics with the molecular-recognition properties of biology to generate hand-held devices that can diagnose diseases at the point-of-care, analyze environmental samples in the field, and assess food safety from the farm to the table. A key challenge is the integration of the labile biological recognition elements (e.g., proteins) at specific device addresses. Here, we report a simple, safe, and generic approach for assembling proteins in response to electrodeimposed electrical signals. This approach relies on the aminopolysaccharide chitosan that can be electrodeposited in response to cathodic signals and then electrochemically activated by anodic signals. The electodeposited and electroactivated chitosan films react with proteins to assemble them with spatial-selectivity and quantitative-control. The evidence presented indicates that the assembled proteins retain their native structure and biological functions. This method for on-demand biofunctionalization of individual electrode addresses should offer a generic approach to assemble proteins for multiplexed analysis.There has been considerable effort to discover mechanisms in which electrode-imposed electrical signals can promote the spatially-selective assembly of proteins at specific addresses. [1,2]

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Uronic Acids in Oligosaccharide Synthesis

Cited by 75 publications

References 149 publications

Integrated Approach to Identify Heparan Sulfate Ligand Requirements of Robo1

Integrated Approach to Identify Heparan Sulfate Ligand Requirements of Robo1

Installation of Electron-Donating Protective Groups, a Strategy for Glycosylating Unreactive Thioglycosyl Acceptors using the Preactivation-Based Glycosylation Method

Reagentless Protein Assembly Triggered by Localized Electrical Signals

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