Browse
Submit Data
Databases
API
Help

Dataset Information

28 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Fluorous supported modular synthesis of heparan sulfate oligosaccharides.

ABSTRACT: The modular synthesis of heparan sulfate fragments is greatly facilitated by employing an anomeric aminopentyl linker protected by a benzyloxycarbonyl group modified by a perfluorodecyl tag, which made it possible to purify highly polar intermediates by fluorous solid phase extraction. This tagging methodology made it also possible to perform repeated glycosylations to drive reactions to completion.

SUBMITTER: Zong C

PROVIDER: S-EPMC3563243 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Fluorous supported modular synthesis of heparan sulfate oligosaccharides.

Zong Chengli C Venot Andre A Dhamale Omkar O Boons Geert-Jan GJ

Organic letters 20130108 2

The modular synthesis of heparan sulfate fragments is greatly facilitated by employing an anomeric aminopentyl linker protected by a benzyloxycarbonyl group modified by a perfluorodecyl tag, which made it possible to purify highly polar intermediates by fluorous solid phase extraction. This tagging methodology made it also possible to perform repeated glycosylations to drive reactions to completion. ...[more]

PMID: 23293947

Similar Datasets

Fluorous-assisted chemoenzymatic synthesis of heparan sulfate oligosaccharides.

Project description:The chemoenzymatic synthesis of heparan sulfate tetrasaccharide (1) and hexasaccharide (2) with a fluorous tag attached at the reducing end is reported. The fluorous tert-butyl dicarbonate ((F)Boc) tag did not interfere with enzymatic recognition for both elongation and specific sulfation, and flash purification was performed by standard fluorous solid-phase extraction (FSPE). Based on an (F)Boc attached disaccharide as acceptor, a series of partial N-sulfated, 6-O-sulfated heparan sulfate oligosaccharides were successfully synthesized employing fluorous techniques.

| S-EPMC3998769 | biostudies-literature

Modular synthesis of heparan sulfate oligosaccharides for structure-activity relationship studies.

Project description:Although hundreds of heparan sulfate binding proteins have been identified and implicated in a myriad of physiological and pathological processes, very little information is known about the ligand requirements for binding and mediating biological activities by these proteins. This difficulty results from a lack of technology for establishing structure-activity relationships, which in turn is due to the structural complexity of natural heparan sulfate (HS) and difficulties of preparing well-defined HS oligosaccharides. To address this deficiency, we developed a modular approach for the parallel combinatorial synthesis of HS oligosaccharides that utilizes a relatively small number of selectively protected disaccharide building blocks, which can easily be converted into glycosyl donors and acceptors. The utility of the modular building blocks has been demonstrated by the preparation of a library of 12 oligosaccharides, which has been employed to probe the structural features of HS for inhibiting the protease, BACE-1. The complex variations in activity with structural changes support the view that important functional information is embedded in HS sequences. Furthermore, the most active derivative provides an attractive lead compound for the preparation of more potent compounds, which may find use as a therapeutic agent for Alzheimer's disease.

| S-EPMC2820250 | biostudies-literature

New glucuronic acid donors for the modular synthesis of heparan sulfate oligosaccharides.

Project description:Although hundreds of heparan sulfate (HS) binding proteins have been implicated in a myriad of physiological and pathological processes, very little information is known about ligand requirements for binding and mediating biological activities by these proteins. We report here a streamlined approach for the preparation of modular disaccharide building blocks that will facilitate the assembly of libraries of HS oligosaccharides for structure-activity relationship studies. In particular, we have found that glucuronic acid donors, which usually perform poorly in glycosylations, can give high yields of coupling products when the C-2 hydroxyl is protected with a permanent 4-acetoxy-2,2-dimethyl butanoyl- (PivOAc) or temporary levulinoyl (Lev) ester and the C-4 hydroxyl modified with a selectively removable 2-methylnaphthyl (Nap) ether. It has been shown that the PivOAc ester can be removed without affecting sulfate esters making it an ideal protecting group for HS oligosaccharide assembly. Iduronic acid donors exhibit more favorable glycosyl donating properties and a compound protected with a Lev ester at C-2 and an Fmoc function at the C-4 hydroxyl gave coupling products in high yield. The new donors avoid post-glycosylation oxidation and therefore allow the facile preparation of modular disaccharide building blocks.

| S-EPMC4009994 | biostudies-literature

Divergent Synthesis of Heparan Sulfate Oligosaccharides.

Project description:Heparan sulfates are implicated in a wide range of biological processes. A major challenge in deciphering their structure and activity relationship is the synthetic difficulties to access diverse heparan sulfate oligosaccharides with well-defined sulfation patterns. In order to expedite the synthesis, a divergent synthetic strategy was developed. By integrating chemical synthesis and two types of O-sulfo transferases, seven different hexasaccharides were obtained from a single hexasaccharide precursor. This approach combined the flexibility of chemical synthesis with the selectivity of enzyme-catalyzed sulfations, thus simplifying the overall synthetic operations. In an attempt to establish structure activity relationships of heparan sulfate binding with its receptor, the synthesized oligosaccharides were incorporated onto a glycan microarray, and their bindings with a growth factor FGF-2 were examined. The unique combination of chemical and enzymatic approaches expanded the capability of oligosaccharide synthesis. In addition, the well-defined heparan sulfate structures helped shine light on the fine substrate specificities of biosynthetic enzymes and confirm the potential sequence of enzymatic reactions in biosynthesis.

| S-EPMC4685427 | biostudies-literature

Controlled Chemoenzymatic Synthesis of Heparan Sulfate Oligosaccharides.

Project description:A chemoenzymatic approach has been developed for the preparation of diverse libraries of heparan sulfate (HS) oligosaccharides. It employs chemically synthesized oligosaccharides having a chemical entity at a GlcN residue, which in unanticipated manners influences the site of modification by NST, C5-Epi/2-OST and 6-OST1 /6-OST3 , thus resulting in oligosaccharides differing in N/O-sulfation and epimerization pattern. The enzymatic transformations defined fine substrate requirements of NST, C5-Epi, 2-OST, and 6-OST.

| S-EPMC5996245 | biostudies-literature

Chemoenzymatic Synthesis of Heparan Sulfate Oligosaccharides having a Domain Structure.

Project description:Heparan sulfate (HS) has a domain structure in which regions that are modified by epimerization and sulfonation (NS domains) are interspersed by unmodified fragments (NA domains). There is data to support that domain organization of HS can regulate binding of proteins, however, such model has been difficult to probe. Here, we report a chemoenzymatic methodology that can provide HS oligosaccharides composed of two or more NS domains separated by NA domains of different length. It is based on the chemical synthesis of a HS oligosaccharide that enzymatically was extended by various GlcA-GlcNAc units and terminated in GlcNAc having an azido moiety at C-6 position. HS oligosaccharides having an azide and alkyne moiety could be assembled by copper catalyzed alkyne-azide cycloaddition to give compounds having various NS domains separated by unsulfonated regions. Competition binding studies showed that the length of an NA domain modulates the binding of the chemokines CCL5 and CXCL8.

| S-EPMC9828060 | biostudies-literature

Chemoenzymatic design of heparan sulfate oligosaccharides.

Project description:Heparan sulfate is a sulfated glycan that exhibits essential physiological functions. Interrogation of the specificity of heparan sulfate-mediated activities demands a library of structurally defined oligosaccharides. Chemical synthesis of large heparan sulfate oligosaccharides remains challenging. We report the synthesis of oligosaccharides with different sulfation patterns and sizes from a disaccharide building block using glycosyltransferases, heparan sulfate C(5)-epimerase, and sulfotransferases. This method offers a generic approach to prepare heparan sulfate oligosaccharides possessing predictable structures.

| S-EPMC2962522 | biostudies-literature

Chemical Synthesis of Δ-4,5 Unsaturated Heparan Sulfate Oligosaccharides for Biomarker Discovery.

Project description:A methodology is described that can provide heparan sulfate oligosaccharides having a Δ4,5-double bond, which are needed as analytical standards and biomarkers for mucopolysaccharidoses. It is based on chemical oligosaccharide synthesis followed by modification of the C-4 hydroxyl of the terminal uronic acid moiety as methanesulfonate. This leaving group is stable under conditions used to remove temporary protecting groups, O-sulfation, and hydrogenolysis. Treatment with NaOH results in elimination of the methanesulfonate and formation of a Δ4,5-double bond.

| S-EPMC10985652 | biostudies-literature

Probing Amyloid β Interactions with Synthetic Heparan Sulfate Oligosaccharides.

Project description:Heparan sulfate (HS) can play important roles in the biology and pathology of amyloid β (Aβ), a hallmark of Alzheimer's disease. To better understand the structure-activity relationship of HS/Aβ interactions, synthetic HS oligosaccharides ranging from tetrasaccharides to decasaccharides have been utilized to study Aβ interactions. Surface plasmon resonance experiments showed that the highly sulfated HS tetrasaccharides bearing full 2-O, 6-O, and N-sulfations exhibited the strongest binding with Aβ among the tetrasaccharides investigated. Elongating the glycan length to hexa- and deca-saccharides significantly enhanced Aβ affinity compared to the corresponding HS tetrasaccharide. Solid state NMR studies of the complexes of Aβ with HS hexa- and deca-saccharides showed most significant chemical shift perturbation in the C-terminus residues of Aβ. The strong binding HS oligosaccharides could reduce the cellular toxicities induced by Aβ. This study provides new insights into HS/Aβ interactions, highlighting how synthetic structurally well-defined HS oligosaccharides can assist in biological understanding of Aβ.

| S-EPMC8444215 | biostudies-literature

Design and Synthesis of 6-O-Phosphorylated Heparan Sulfate Oligosaccharides to Inhibit Amyloid β Aggregation.

Project description:Dysregulation of amyloidogenic proteins and their abnormal processing and deposition in tissues cause systemic and localized amyloidosis. Formation of amyloid β (Aβ) fibrils that deposit as amyloid plaques in Alzheimer's disease (AD) brains is an earliest pathological hallmark. The polysulfated heparan sulfate (HS)/heparin (HP) is one of the non-protein components of Aβ deposits that not only modulates Aβ aggregation, but also acts as a receptor for Aβ fibrils to mediate their cytotoxicity. Interfering with the interaction between HS/HP and Aβ could be a therapeutic strategy to arrest amyloidosis. Here we have synthesized the 6-O-phosphorylated HS/HP oligosaccharides and reported their competitive effects on the inhibition of HP-mediated Aβ fibril formation in vitro using a thioflavin T fluorescence assay and a tapping mode atomic force microscopy.

| S-EPMC9401075 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data