Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Developments in Mass Spectrometry for Glycosaminoglycan Analysis: A Review.

ABSTRACT: This review covers recent developments in glycosaminoglycan (GAG) analysis via mass spectrometry (MS). GAGs participate in a variety of biological functions, including cellular communication, wound healing, and anticoagulation, and are important targets for structural characterization. GAGs exhibit a diverse range of structural features due to the variety of O- and N-sulfation modifications and uronic acid C-5 epimerization that can occur, making their analysis a challenging target. Mass spectrometry approaches to the structure assignment of GAGs have been widely investigated, and new methodologies remain the subject of development. Advances in sample preparation, tandem MS techniques (MS/MS), online separations, and automated analysis software have advanced the field of GAG analysis. These recent developments have led to remarkable improvements in the precision and time efficiency for the structural characterization of GAGs.

SUBMITTER: Pepi LE

PROVIDER: S-EPMC8724624 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Developments in Mass Spectrometry for Glycosaminoglycan Analysis: A Review.

Pepi Lauren E LE Sanderson Patience P Stickney Morgan M Amster I Jonathan IJ

Molecular & cellular proteomics : MCP 20210106

This review covers recent developments in glycosaminoglycan (GAG) analysis via mass spectrometry (MS). GAGs participate in a variety of biological functions, including cellular communication, wound healing, and anticoagulation, and are important targets for structural characterization. GAGs exhibit a diverse range of structural features due to the variety of O- and N-sulfation modifications and uronic acid C-5 epimerization that can occur, making their analysis a challenging target. Mass spectro ...[more]

PMID: 32938749

Similar Datasets

Recent technological developments for native mass spectrometry.

Project description:Native mass spectrometry (MS), the analysis of proteins and protein complexes from solutions that stabilize native solution structures, is a rapidly expanding area. There is strong evidence supporting the retention of proteins' native folds in the absence of solvent under the experimental timescales of MS experiments. Therefore, instrumentation has been developed to use gas-phase native-like protein ions to exploit the speed, sensitivity, and selectivity of mass spectrometry approaches to solve emerging problems in structural biology. This article reviews some of the recent advances and applications in gas-phase instrumentation for structural proteomics.

| S-EPMC9219587 | biostudies-literature

Analysis of Total Human Urinary Glycosaminoglycan Disaccharides by Liquid Chromatography-Tandem Mass Spectrometry.

Project description:The determination of complex analytes, present at low concentrations, in biological fluids poses a difficult challenge. This study relies on an optimized method of recovery, enzymatic treatment, and disaccharide analysis by liquid chromatography-tandem mass spectrometry to rapidly determine low concentrations of glycosaminoglycans in human urine. The approach utilizes multiple reaction monitoring (MRM) of glycosaminoglycan disaccharides obtained from treating urine samples with recombinant heparin lyases and chondroitin lyase. This rapid and sensitive method allows the analysis of glycosaminoglycan content and disaccharide composition in urine samples having concentrations 10- to 100-fold lower than those typically analyzed from patients with metabolic diseases, such as mucopolysaccharidosis. The current method facilitates the analysis low (ng/mL) levels of urinary glycosaminoglycans present in healthy individuals and in patients with pathological conditions, such as inflammation and cancers, that can subtly alter glycosaminoglycan content and composition.

| S-EPMC4822829 | biostudies-literature

Disaccharide analysis of glycosaminoglycan mixtures by ultra-high-performance liquid chromatography-mass spectrometry.

Project description:Glycosaminoglycans are a family of polysaccharides widely distributed in all eukaryotic cells. These polyanionic, linear chain polysaccharides are composed of repeating disaccharide units that are often differentially substituted with sulfo groups. The diversity of glycosaminoglycan structures in cells, tissues and among different organisms reflect their functional an evolutionary importance. Glycosaminoglycan composition and structure also changes in development, aging and in disease progression, making their accurate and reliable analysis a critical, albeit, challenging endeavor. Quantitative disaccharide compositional analysis is one of the primary ways to characterize glycosaminoglycan composition and structure and has a direct relationship with glycosaminoglycan biological functions. In this study, glycosaminoglycan disaccharides, prepared from heparan sulfate/heparin, chondroitin sulfate/dermatan sulfate and neutral hyaluronic acid using multiple polysaccharide lyases, were fluorescently labeled with 2-aminoacridone, fractionated into 17 well-resolved components by reverse-phase ultra-performance liquid chromatography, and analyzed by electrospray ionization mass spectrometry. This analysis was successfully applied to cell, tissue, and biological fluid samples for the picomole level detection of glycosaminoglycan composition and structure.

| S-EPMC3268819 | biostudies-literature

Capillary Electrophoresis Mass Spectrometry: Developments and Applications for Enantioselective Analysis from 2011-2020.

Project description:It is now more than 25 years since the first report of enantioselective analysis by capillary electrophoresis-mass spectrometry (CE-MS) appeared. This article reviews the power of chiral CE-MS in resolving issues on the use of chiral selector incompatibility with MS and poor detectability encountered for chiral compounds by UV detection. The review begins with the general principles, requirements, and critical aspects of chiral CE-MS instrumentation. Next, the review provides a survey of MS-compatible chiral selectors (CSs) reported during the past decade, and the key achievements encountered in the time period using these CSs. Within the context of the strategies used to combine CE and MS, special attention is paid to the approaches that feature partial filling technique, counter-migration techniques, and direct use of CS, such as molecular micelles. In particular, the development and application of moving and fixed CS for EKC-MS, MEKC-MS, and CEC-MS demonstrate how various chiral compounds analyses were solved in a simple and elegant way during the 2010-2020 review period. The most noteworthy applications in the determination of chiral compounds are critically examined. The operating analytical conditions are detailed in the Tables, and the authors provide commentary on future trends of chiral separations by CE-MS.

| S-EPMC9268241 | biostudies-literature

MMP qualitative and quantitative mass spectrometry

Project description:Methanococcus maripaludis is a methanogenic archaeon. Within its genome, there are two operons for membrane associated hydrogenases, eha and ehb. To investigate the regulation of ehb on the cell, an S40 mutant was constructed in such a way that a portion of the ehb operon was replaced by pac cassette in the wild type parental strain S2 (done by Whitman's group at the University of Georgia). The S40 and S2 strains were grown in 14N and 15N media with acetate separately. A biological replicate was made by switching the media. Mass spectrometry based quantitative proteomics were done on the mixtures to investigate the differences in expression patterns between S40 and S2. Keywords: isotope labeling mass spectrometry, quantitative proteomics

2005-09-20 | GSE2744 | GEO

Online Capillary Zone Electrophoresis Negative Electron Transfer Dissociation Tandem Mass Spectrometry of Glycosaminoglycan Mixtures.

Project description:Glycosaminoglycans (GAGs) are important biological molecules that are highly anionic and occur in nature as complex mixtures. A platform that combines capillary zone electrophoresis (CZE) separations with mass spectrometry (MS) and gas-phase sequencing by using negative electron transfer dissociation (NETD) is shown to be efficacious for the structural analysis of GAG mixtures. CZE is a separation method well suited to the highly negatively charged nature of GAGs. NETD is an electron-based ion activation method that enables the generation of informative fragments with retention of the labile sulfate half-ester modification that determine specific GAG function. Here we combine for the first time NETD and CZE for assigning the structures of GAG oligomers present in mixtures. The speed of ion activation by NETD is found to couple well with the narrow peaks resulting from CZE migration. The platform was optimized with mixtures of GAG tetrasaccharide standards. The potential of the platform is demonstrated by the analysis of enoxaparin, a complex mixture of low molecular weight heparins, which was separated by CZE within 30 minutes and characterized by NETD MS/MS in one online experiment. 37 unique molecular compositions have been identified in enoxaparin using CZE-MS and 9 structures have been assigned with CZE-NETD-MS/MS.

| S-EPMC7343235 | biostudies-literature

Peracylation Coupled with Tandem Mass Spectrometry for Structural Sequencing of Sulfated Glycosaminoglycan Mixtures without Depolymerization.

Project description:The structures of glycosaminoglycans (GAGs), especially the patterns of modification, are crucial to modulate interactions with various protein targets. It is very challenging to determine the fine structures using liquid chromatography-mass spectrometry (LC-MS) due in large part to the gas-phase sulfate losses upon collisional activation. Previously, our group reported a method for fine structure analysis that required permethylation of the GAG oligosaccharide. However, uncontrolled depolymerization during the permethylation process due to esterification of uronic acid lowers the reliability of the method to resolve structures of GAGs, especially for larger oligosaccharides. Here, we describe a simplified derivatization method using propionylation and desulfation. The oligosaccharides have all hydroxyl and amine groups protected with propionyl groups and then have sulfate groups removed to generate unprotected hydroxyl and amine groups at all sites that were previously sulfated. This derivatized oligosaccharide generates informative fragments during collision-induced dissociation that resolve the original sulfation patterns. This method is demonstrated to enable accurate determination of sulfation patterns of even the highly sulfated pentasaccharide fondaparinux by MS2 and MS3. Using a mixture of dp6 from porcine heparin, we demonstrate that this method allows for structural characterization of complex mixtures, including clear chromatographic separation and sequencing of structural isomers, all at high yields without evidence of depolymerization. This represents a marked improvement in the reliability to structurally characterize GAG oligosaccharides over permethylation-based derivatization schemes.

| S-EPMC7664153 | biostudies-literature

Mass Spectrometry Reveals a Multifaceted Role of Glycosaminoglycan Chains in Factor Xa Inactivation by Antithrombin.

Project description:Factor Xa (fXa) inhibition by antithrombin (AT) enabled by heparin or heparan sulfate is critical for controlling blood coagulation. AT activation by heparin has been investigated extensively, while interaction of heparin with trapped AT/fXa intermediates has received relatively little attention. We use native electrospray ionization mass spectrometry to study the role of heparin chains of varying length [hexa-, octa-, deca-, and eicosasaccharides (dp6, dp8, dp10, and dp20, respectively)] in AT/fXa complex assembly. Despite being critical promoters of AT/Xa binding, shorter heparin chains are excluded from the final products (trapped intermediates). However, replacement of short heparin segments with dp20 gives rise to a prominent ionic signal of ternary complexes. These species are also observed when the trapped intermediate is initially prepared in the presence of a short oligoheparin (dp6), followed by addition of a longer heparin chain (dp20), indicating that binding of heparin to AT/fXa complexes takes place after the inhibition event. The importance of the heparin chain length for its ability to associate with the trapped intermediate suggests that the binding likely occurs in a bidentate fashion (where two distinct segments of oligoheparin make contacts with the protein components, while the part of the chain separating these two segments is extended into solution to minimize electrostatic repulsion). This model is corroborated by both molecular dynamics simulations with an explicit solvent and ion mobility measurements in the gas phase. The observed post-inhibition binding of heparin to the trapped AT/fXa intermediates hints at the likely role played by heparan sulfate in their catabolism.

| S-EPMC6445383 | biostudies-literature

Mass Spectrometry Imaging with Trapped Ion Mobility Spectrometry Enables Spatially Resolved Chondroitin, Dermatan, and Hyaluronan Glycosaminoglycan Oligosaccharide Analysis <i>In Situ</i>.

Project description:Previously, spatially resolved analysis of glycosaminoglycans (GAGs), by type and sulfation state, was unobtainable. Here, we describe a mass spectrometry imaging (MSI) approach which enables the detection, identification, localization, and profiling of GAG oligosaccharides directly from retinal tissue. Through in situ treatment of tissues with relevant chondroitinase enzymes, we liberate and spatially resolve chondroitin, dermatan, and hyaluronan from disaccharides through to hexasaccharides, directly from tissue sections. We demonstrate the separation of isomeric GAG oligosaccharide ions at different histologically relevant regions using trapped ion mobility spectrometry (TIMS). This paper describes the first spatially resolved analysis of multiple GAGs and their oligosaccharide sulfation state(s) directly from tissues.

| S-EPMC11561879 | biostudies-literature

Normalization of glycosaminoglycan-derived disaccharides detected by tandem mass spectrometry assay for the diagnosis of mucopolysaccharidosis.

Project description:Mucopolysaccharidosis (MPS) is caused by the deficiency of a specific hydrolytic enzyme that catalyzes the step-wise degradation of glycosaminoglycans (GAGs). In this study, we propose an empirical method to calculate levels of GAG-derived disaccharides based on the quantity (peak areas) of chondroitin sulfate (CS) with the aim of making a diagnosis of MPS more accurate and reducing the occurrence of false positive and false negative results. In this study, levels of urinary GAG-derived disaccharides were measured in 67 patients with different types of MPS and 165 controls without MPS using a tandem mass spectrometry assay. Two different methods of reporting GAG-derived disaccharides were assessed; normalization to urinary CS (in μg/mL), and normalization to μg/mg creatinine. CS-normalization yielded more consistent values than creatinine-normalization. In particular, levels of urinary dermatan sulfate (DS), heparan sulfate (HS), and keratan sulfate (KS) significantly varied because of changes in urine creatinine levels, which were proportional to age but inversely proportional to DS, HS, and KS measurements. Using CS-normalization revealed the actual status of DS, HS, and KS without the influence of factors such as age, urine creatinine, and other physiological conditions. It could discriminate between the patients with MPS and controls without MPS, and also to evaluate changes in GAG levels pre- and post-enzyme replacement therapy.

| S-EPMC6656773 | 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