Tandem mass spectrometric strategies for determination of sulfation positions and uronic acid epimerization in chondroitin sulfate oligosaccharides

Zaia, Joseph; Li, Xue Qing; Chan, Shiu Yung; Costello, Catherine E.

doi:10.1016/s1044-0305(03)00541-5

Cited by 96 publications

(108 citation statements)

References 51 publications

(65 reference statements)

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“…The relative derivatization yields were found via mass spectrometry on a quadrupole-ion trap mass spectrometer (QITMS). Samples were sprayed in a 30% MeOH, 0.2% NH 4 OH solution under nano-spray conditions (24). Mass spectra revealed peaks at m/z 459.1 and 578.8 representing the unlabeled and the labeled CS disaccharides, respectively.…”

Section: Derivatization Of Oligosaccharides With D 0 -And D 4 -2-aamentioning

confidence: 99%

Glycoform Quantification of Chondroitin/Dermatan Sulfate Using a Liquid Chromatography−Tandem Mass Spectrometry Platform

2006

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Chondroitin sulfate (CS) is a glycosaminoglycan consisting of repeating uronic acid, Nacetylgalactosamine disaccharide units [(HexAβ/α(1-3) GalNAcβ (1-4)] n. CS chains are polydisperse with respect to chain length, sulfate content and glucuronic acid epimerization content, resulting in a distribution of glycoforms for a chain bound to any given serine residue. Usually, CS glycoforms exist, differing in sulfation position and uronic acid epimerization. This work introduces a novel LC/MS/MS platform for the quantification of mixtures of CS oligosaccharides. The CS polysaccharides were partially depolymerized and labeled with either the light (d 0 ) or heavy (d 4 ) form of 2-anthranilic acid (2-AA). Excess reagent was removed and mixtures of the CS standard (d 0 ) and unknown (d 4 ) were made. The CS mixture was subjected to size exclusion chromatography (SEC) with on-line electrospray ionization mass spectrometrometric detection in the negative ion mode. Tandem mass spectra were acquired and quantification of unknown samples within the mixture was made using relative ion abundances of specific diagnostic ions. High accuracy and precision of the glycomics platform were demonstrated using glycoform mixtures made from standard CS preparations. The CS glycoform analysis method was then applied to cartilage extract, versican, and several dermatan sulfate preparations. This work presents the first application of a glycomics platform for the quantification of CS oligosaccharide mixtures to obtain specific information on the positions of GalNAc sulfation and uronic acid epimerization.Glycomics is applied biology and chemistry that focuses on the structure and function of carbohydrates. Carbohydrates have vital functions in the body; in particular, glycosylation serves to diversify protein functions. Despite their abundance, much less information is known about carbohydrates, as compared to genes and proteins, largely due to the absence of a simple code that determines their structures. Mass spectrometry (MS), high performance liquid chromatography and other analytical tools have advanced rapidly to support the growth of biomolecular applications in the field of proteomics. However, technologies and methods to address the most challenging problems in glycomics, particularly with respect to glycoform quantitative measurements, remain undeveloped.Glycosaminoglycans (GAGs) are linear polysaccharides that consist of repeating disaccharide units that are attached to proteoglycan core proteins on adherent animal cell surfaces and in extracellular matrices (1-5). GAGs play significant roles in the modulation of cellular signals through interactions with proteins, including growth factors and growth factor receptors (6-8). They mediate cell-cell and cell-matrix interactions and are crucial to cell development and

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Section: Derivatization Of Oligosaccharides With D 0 -And D 4 -2-aamentioning

confidence: 99%

Glycoform Quantification of Chondroitin/Dermatan Sulfate Using a Liquid Chromatography−Tandem Mass Spectrometry Platform

2006

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“…As the epimeric state of the hexuronic acid residues is thought to influence biological activity, it is important to be able to analyze GAG oligosaccharides which contain internal hexuronic acid residues that retain their chirality. Although tandem mass spectrometry is typically insensitive to stereochemistry, MS/MS of a series of isobaric CS samples has been shown to distinguish IdoA from GlcA as well as distinguish 4S-from 6S-sulfation based on the relative abundance of specific product ions [22].…”

mentioning

confidence: 99%

Electron detachment dissociation of dermatan sulfate oligosaccharides

Wolff

Laremore

Busch

et al. 2008

J. Am. Soc. Mass Spectrom.

108

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The structural characterization of glycosaminoglycans (GAG) oligosaccharides has been a long-standing challenge in the field of mass spectrometry. In this work, we present the application of electron detachment dissociation (EDD) Fourier transform mass spectrometry to the analysis of dermatan sulfate (DS) oligosaccharides up to 10 residues long. The EDD mass spectra of DS oligosaccharides were compared with their infrared multiphoton dissociation (IRMPD) mass spectra. EDD produces more abundant fragmentation than IRMPD with far less loss of SO 3 from labile sulfate modifications. EDD cleaves all glycosidic bonds, yielding both conventional glycosidic bond fragmentation as well as satellite peaks resulting from the additional loss of 1 or 2 hydrogen atoms. EDD also yields more cross-ring fragmentation than IRMPD. For EDD, abundant cross-ring fragmentation in the form of A-and X-ions is observed, with 1,5 X n cleavages occurring for all IdoA residues and many of the GalNAc4S residues, except at the reducing and nonreducing ends. In contrast, IRMPD produces only A-type cross-ring fragmentation for long oligosaccharides (dp6 -dp10). As all the structurally informative fragment ions observed by IRMPD appear as a subset of the peaks found in the EDD mass spectrum, EDD shows great potential for the characterization of GAG oligosaccharides using a single tandem mass spectrometry experiment. (J

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“…Besides, closed-ring derivatives provided improved structural information on linkage and anomeric configuration. Unreduced glycosylamine derivatives were also preferred over reduced derivatives for the purposes of determining sulfation and uronic acid positions in chondroitin sulfate saccharides [20].…”

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confidence: 99%

Influence of the labeling group on ionization and fragmentation of carbohydrates in mass spectrometry

Lattová

Snovida

Perreault

et al. 2005

J. Am. Soc. Mass Spectrom.

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The ionization and fragmentation behaviors of carbohydrate derivatives prepared by reaction with 2-aminobenzamide (AB), 1-phenyl-3-methyl-5-pyrazolone (PMP), and phenylhydrazine (PHN) were compared under identical mass spectrometric conditions. It has been shown that the intensities of signals in MS spectra depend on the kind of saccharides investigated and reducing end labels used. PMP sialyllactose, when ionized by ESI/MALDI, produced a mixture of ϩ ions. PMP-and reduced AB-sialyllactose produced only Y-type fragment ions under both MS/MS sources. In the electrospray ionization (ESI)-MS/MS spectrum of PHN-sialyllactose, abundant ions corresponded to B, Z cleavages and in its MALDI-MS/MS spectrum, the abundant ions were consistent with Y glycosidic cleavages with the concurrence of B, C, and cross-ring fragment ions. In the MALDI-MS spectra of oligosaccharides acquired immediately after derivatization, it was possible to detect only PHN derivatives. After purification, spectra of all three types of derivatives showed high signal-to-noise ratios with the most abundant ions observed for AB reduced saccharides. [M ϩ Na] ϩ ions were the dominant products and their fragmentation patterns were influenced by the type of the labeling and the kind of oligosaccharide considered. In the MALDI-PSD and -MS/MS spectra of AB-derivatized glycans, higher m/z fragment ions corresponded to B and Y cleavages and the loss of bisecting GlcNAc appeared as a weak signal or was not detected at all. Fragmentation patterns observed in the spectra of hybrid/complex PHN and PMP glycans were more comparable-higher m/z fragments corresponded to B and C glycosidic cleavages. For PHN glycans, the abundance of ions resulting from the loss of bisecting GlcNAc depended on the number of residues linked to the 6-positioned mannose. Also, PHN and PMP derivatives produced cross-ring cleavages with abundances higher than observed in the spectra of AB derivatized oligosaccharides. For high-mannose glycans, the most informative cleavages were provided by AB and PHN type of labeling. Glycosylation is also highly sensitive to alterations of cellular function, and altered protein glycosylation is diagnostic of a number of disease states including, for example, rheumatoid arthritis and cancer [3]. Therefore, the growing interest in understanding the biological functions of carbohydrates has stimulated the development of methods for their improved analysis.In order to detect saccharides by UV/fluorescence and also to ease their characterization by mass spectrometry (MS), introducing a chromophore into the molecules has received increasing attention. In this respect, a large number of derivatization procedures for mono-and oligosaccharides have been described in the literature, most of which have been detailed in a recent review [4]. For example, 2-aminoacridine (2-AMAC) as a sensitive fluorophore, has been used for the detection of monosaccharides, and of neutral and charged oligosaccharides by electrospray ionization (ESI) and matrix-

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Tandem mass spectrometric strategies for determination of sulfation positions and uronic acid epimerization in chondroitin sulfate oligosaccharides

Cited by 96 publications

References 51 publications

Glycoform Quantification of Chondroitin/Dermatan Sulfate Using a Liquid Chromatography−Tandem Mass Spectrometry Platform

Glycoform Quantification of Chondroitin/Dermatan Sulfate Using a Liquid Chromatography−Tandem Mass Spectrometry Platform

Electron detachment dissociation of dermatan sulfate oligosaccharides

Influence of the labeling group on ionization and fragmentation of carbohydrates in mass spectrometry

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