Browse
Submit Data
Databases
API
Help

Dataset Information

48 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Automated synthesis of sialylated oligosaccharides.

ABSTRACT: Sialic acid-containing glycans play a major role in cell-surface interactions with external partners such as cells and viruses. Straightforward access to sialosides is required in order to study their biological functions on a molecular level. Here, automated oligosaccharide synthesis was used to facilitate the preparation of this class of biomolecules. Our strategy relies on novel sialyl α-(2→3) and α-(2→6) galactosyl imidates, which, used in combination with the automated platform, provided rapid access to a small library of conjugation-ready sialosides of biological relevance.

SUBMITTER: Esposito D

PROVIDER: S-EPMC3510992 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Automated synthesis of sialylated oligosaccharides.

Esposito Davide D Hurevich Mattan M Castagner Bastien B Wang Cheng-Chung CC Seeberger Peter H PH

Beilstein journal of organic chemistry 20120921

Sialic acid-containing glycans play a major role in cell-surface interactions with external partners such as cells and viruses. Straightforward access to sialosides is required in order to study their biological functions on a molecular level. Here, automated oligosaccharide synthesis was used to facilitate the preparation of this class of biomolecules. Our strategy relies on novel sialyl α-(2→3) and α-(2→6) galactosyl imidates, which, used in combination with the automated platform, provided ra ...[more]

PMID: 23209492

Similar Datasets

Synthesis and Characterization of Sialylated Lactose- and Lactulose-Derived Oligosaccharides by Trypanosoma cruzi Trans-sialidase.

Project description:Sialylated oligosaccharides contribute 12.6-21.9% of total free oligosaccharides in human milk ( hMOS). These acidic hMOS possess prebiotic properties and display antiadhesive effects against pathogenic bacteria. Only limited amounts of sialylated hMOS are currently available. The aim of our work is to enzymatically synthesize sialylated oligosaccharides mimicking hMOS functionality. In this study, we tested mixtures of glucosylated-lactose (GL34), galactosylated-lactulose (LGOS), and galacto-oligosaccharide (Vivinal GOS) molecules, as trans-sialylation acceptor substrates. The recombinant trans-sialidase enzyme from Trypanosoma cruzi (TcTS) was used for enzymatic decoration, transferring (?2?3)-linked sialic acid from donor substrates to nonreducing terminal ?-galactopyranosyl units of these acceptor substrates. The GL34 F2 2-Glc-Lac compound with an accessible terminal galactosyl residue was sialylated efficiently (conversion degree of 47.6%). TcTS sialylated at least 5 LGOS structures and 11 Vivinal GOS DP3-4 compounds. The newly synthesized sialylated oligosaccharides are interesting as potential hMOS mimics for applications in biomedical and functional-food products.

| S-EPMC6581423 | biostudies-literature

Automated solid-phase synthesis of oligosaccharides containing sialic acids.

Project description:A sialic acid glycosyl phosphate building block was designed and synthesized. This building block was used to prepare ?-sialylated oligosaccharides by automated solid-phase synthesis selectively.

| S-EPMC4464161 | biostudies-literature

Electron detachment dissociation of fluorescently labeled sialylated oligosaccharides.

Project description:We explored the application of electron detachment dissociation (EDD) and infrared multiphoton dissociation (IRMPD) tandem mass spectrometry to fluorescently labeled sialylated oligosaccharides. Standard sialylated oligosaccharides and a sialylated N-linked glycan released from human transferrin were investigated. EDD yielded extensive glycosidic cleavages and cross-ring cleavages in all cases studied, consistently providing complementary structural information compared with infrared multiphoton dissociation. Neutral losses and satellite ions such as C-2H ions were also observed following EDD. In addition, we examined the influence of different fluorescent labels. The acidic label 2-aminobenzoic acid (2-AA) enhanced signal abundance in negative-ion mode. However, few cross-ring fragments were observed for 2-AA-labeled oligosaccharides. The neutral label 2-aminobenzamide (2-AB) resulted in more cross-ring cleavages compared with 2-AA-labeled species, but not as extensive fragmentation as for native oligosaccharides, likely resulting from altered negative charge locations from introduction of the fluorescent tag.

| S-EPMC3288116 | biostudies-literature

Digital microfluidics-engaged automated enzymatic degradation and synthesis of oligosaccharides.

Project description:Glycans are an important group of natural biopolymers, which not only play the role of a major biological energy resource but also as signaling molecules. As a result, structural characterization or sequencing of glycans, as well as targeted synthesis of glycans, is of great interest for understanding their structure-function relationship. However, this generally involves tedious manual operations and high reagent consumptions, which are the main technical bottlenecks retarding the advances of both automatic glycan sequencing and synthesis. Until now, automated enzymatic glycan sequencers or synthesizers are still not available on the market. In this study, to promote the development of automation in glycan sequencing or synthesis, first, programmed degradation and synthesis of glycans catalyzed by enzymes were successfully conducted on a digital microfluidic (DMF) device by using microdroplets as microreactors. In order to develop automatic glycan synthesizers and sequencers, a strategy integrating enzymatic oligosaccharide degradation or synthesis and magnetic manipulation to realize the separation and purification process after enzymatic reactions was designed and performed on DMF. An automatic process for enzymatic degradation of tetra-N-acetyl chitotetraose was achieved. Furthermore, the two-step enzymatic synthesis of lacto-N-tetraose was successfully and efficiently completed on the DMF platform. This work demonstrated here would open the door to further develop automatic enzymatic glycan synthesizers or sequencers based on DMF.

| S-EPMC10320006 | biostudies-literature

Sialylated milk oligosaccharides impact bone growth

Project description:Mechanisms by which sialylated milk oligosaccharides impact bone growth in a gnotobiotic mouse model of infant undernutrition

| PRJEB29697 | ENA

Annotation and structural analysis of sialylated human milk oligosaccharides.

Project description:Sialylated human milk oligosaccharides (SHMOs) are important components of human milk oligosaccharides. Sialic acids are typically found on the nonreducing end and are known binding sites for pathogens and aid in neonates' brain development. Due to their negative charge and hydrophilic nature, they also help modulate cell-cell interactions. It has also been shown that sialic acids are involved in regulating the immune response and aid in brain development. In this study, the enriched SHMOs from pooled milk sample were analyzed by HPLC-Chip/QTOF MS. The instrument employs a microchip-based nano-LC column packed with porous graphitized carbon (PGC) to provide excellent isomer separation for SHMOs with highly reproducible retention time. The precursor ions were further examined with collision-induced dissociation (CID). By applying the proper collision energy, isomers can be readily differentiated by diagnostic peaks and characteristic fragmentation patterns. A set of 30 SHMO structures with retention times, accurate masses, and MS/MS spectra was deduced and incorporated into an HMO library. When combined with previously determined neutral components, a library with over 70 structures is obtained allowing high-throughput oligosaccharide structure identification.

| S-EPMC3033989 | biostudies-literature

Fucosylated but not sialylated milk oligosaccharides diminish colon motor contractions.

Project description:Human milk oligosaccharides (HMO) are being studied by different groups exploring a broad range of potential beneficial effects to the breastfed infant. Many of these effects have been attributed to a growth promotion effect on certain gut organisms such as bifidobacteria. Additionally, evidence indicates that HMO are able to directly promote positive changes in gut epithelium and immune responses under certain conditions. This study utilizes a standardized ex vivo murine colon preparation to examine the effects of sialylated, fucosylated and other HMO on gut motor contractions. Only the fucosylated molecules, 2'FL and 3'FL, decreased contractility in a concentration dependent fashion. On the basis of IC50 determinations 3'FL was greater than 2 times more effective than 2'FL. The HMO 3'SL and 6'SL, lacto-N-neotetraose (LNnT), and galactooligosaccharides (GOS) elicited no effects. Lactose was used as a negative control. Fucosylation seems to underlie this functional regulation of gut contractility by oligosaccharides, and L-fucose, while it was also capable of reducing contractility, was substantially less effective than 3'FL and 2'FL. These results suggest that specific HMO are unlikely to be having these effects via bifidogenesis, but though direct action on neuronally dependent gut migrating motor complexes is likely and fucosylation is important in providing this function, we cannot conclusively shown that this is not indirectly mediated. Furthermore they support the possibility that fucosylated sugars and fucose might be useful as therapeutic or preventative adjuncts in disorders of gut motility, and possibly also have beneficial central nervous system effects.

| S-EPMC3788724 | biostudies-other

Crystal structure of reovirus attachment protein ?1 in complex with sialylated oligosaccharides.

Project description:Many viruses attach to target cells by binding to cell-surface glycans. To gain a better understanding of strategies used by viruses to engage carbohydrate receptors, we determined the crystal structures of reovirus attachment protein ?1 in complex with ?-2,3-sialyllactose, ?-2,6-sialyllactose, and ?-2,8-di-siallylactose. All three oligosaccharides terminate in sialic acid, which serves as a receptor for the reovirus serotype studied here. The overall structure of ?1 resembles an elongated, filamentous trimer. It contains a globular head featuring a compact ?-barrel, and a fibrous extension formed by seven repeating units of a triple ?-spiral that is interrupted near its midpoint by a short ?-helical coiled coil. The carbohydrate-binding site is located between ?-spiral repeats two and three, distal from the head. In all three complexes, the terminal sialic acid forms almost all of the contacts with ?1 in an identical manner, while the remaining components of the oligosaccharides make little or no contacts. We used this structural information to guide mutagenesis studies to identify residues in ?1 that functionally engage sialic acid by assessing hemagglutination capacity and growth in murine erythroleukemia cells, which require sialic acid binding for productive infection. Our studies using ?1 mutant viruses reveal that residues 198, 202, 203, 204, and 205 are required for functional binding to sialic acid by reovirus. These findings provide insight into mechanisms of reovirus attachment to cell-surface glycans and contribute to an understanding of carbohydrate binding by viruses. They also establish a filamentous, trimeric carbohydrate-binding module that could potentially be used to endow other trimeric proteins with carbohydrate-binding properties.

| S-EPMC3150272 | biostudies-literature

Sialylated Milk Oligosaccharides Promote Microbiota-Dependent Growth in Models of Infant Undernutrition.

Project description:Identifying interventions that more effectively promote healthy growth of children with undernutrition is a pressing global health goal. Analysis of human milk oligosaccharides (HMOs) from 6-month-postpartum mothers in two Malawian birth cohorts revealed that sialylated HMOs are significantly less abundant in those with severely stunted infants. To explore this association, we colonized young germ-free mice with a consortium of bacterial strains cultured from the fecal microbiota of a 6-month-old stunted Malawian infant and fed recipient animals a prototypic Malawian diet with or without purified sialylated bovine milk oligosaccharides (S-BMO). S-BMO produced a microbiota-dependent augmentation of lean body mass gain, changed bone morphology, and altered liver, muscle, and brain metabolism in ways indicative of a greater ability to utilize nutrients for anabolism. These effects were also documented in gnotobiotic piglets using the same consortium and Malawian diet. These preclinical models indicate a causal, microbiota-dependent relationship between S-BMO and growth promotion.

| S-EPMC4793393 | biostudies-literature

Traceless Photolabile Linker Expedites the Chemical Synthesis of Complex Oligosaccharides by Automated Glycan Assembly.

Project description:Automated glycan assembly (AGA) aims at accelerating access to synthetic oligosaccharides to meet the demand for defined glycans as tools for molecular glycobiology. The linkers used to connect the growing glycan chain to the solid support play a pivotal role in the synthesis strategy as they determine all chemical conditions used during the synthesis and the form of the glycan obtained at the end of it. Here, we describe a traceless photolabile linker used to prepare carbohydrates with a free reducing end. Modification of the o-nitrobenzyl scaffold of the linker is key to high yields and compatibility with the AGA workflow. The assembly of an asymmetrical biantennary N-glycan from oligosaccharide fragments prepared by AGA and linear as well as branched β-oligoglucans is described to illustrate the power of the method. These substrates will serve as standards and biomarkers to examine the unique specificity of glycosyl hydrolases.

| S-EPMC6750752 | 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