Automated chip-nanoelectrospray mass spectrometry for glycourinomics in Schindler disease type I

Sârbu, Mirela; Robu, Adrian; Peter‐Katalinić, Jasna; Zamfir, Alina D.

doi:10.1016/j.carres.2014.08.014

Cited by 8 publications

(16 citation statements)

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“…This ion corroborates for the order of the building blocks in the internal HexHexHexNAcHexNAc sequence. The identified fragment ions in MS 2 and MS 3 document the linkages corresponding to core 2 type of O ‐glycosylation structure, in agreement with the previously acquired knowledge on these substrates …”

Section: Resultssupporting

confidence: 88%

“…Fucosylated heptadecasaccharide Neu5Ac 3 FucHex 7 HexNAc 6 having the molecular weight of 3390.2006, identified as [M − 3H + ] 3− at m / z 1129.0729, is the longest free glycan detected. While Neu5AcHexHexNAc trisaccharide is a structure already known and well characterized in the urine of several Schindler disease patients and healthy persons, Neu5Ac 3 FucHex 7 HexNAc 6 was for the first time discovered in the present study as associated to human urine (Table ). Before, the longest glycan chain ever reported in human urine, in particular in the urine of the Schindler disease patients, was the pentadecasaccharide Neu5Ac 7 Hex 4 HexNAc 4 found linked to Ser and Thr in an approach involving QTOF MS and fully automated chip‐based nanoelectrospray ionization …”

Section: Resultsmentioning

confidence: 56%

“…Moreover, in the last years, to separate and afterwards analyze the complex urine glycopeptide mixtures, simplify the sample preparation procedures and reduce the running costs, capillary electrophoresis technique in online and offline coupling with MS was applied for compositional mapping and structural investigation of various fractions from the urine of Schindler disease type I patients . An accurate comparative screening of Schindler disease patient urine versus healthy control urine based on fully automated chip‐nanoelectrospray ionization (nanoESI) MS, collision‐induced dissociation (CID) quadrupole time‐of‐flight mass spectrometry (QTOF MS) has been recently performed as well . All these studies demonstrated a few fold increases in concentration and number of different O ‐glycopeptide species in patient urine.…”

Section: Introductionmentioning

confidence: 99%

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Identification and structural characterization of novel O‐ and N‐glycoforms in the urine of a Schindler disease patient by Orbitrap mass spectrometry

et al. 2015

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Schindler disease is an inherited metabolic disorder caused by the deficient activity of α-N-acetylgalactosaminidase enzyme. An accurate diagnosis requires, besides clinical examination, complex and costly biochemical and molecular genetic tests. In the last years, mass spectrometry (MS) based on nanofluidics and high-resolution instruments has become a successful alternative for disease diagnosis based on the investigation of O-glycopeptides in patient urine. A complex mixture of glycoforms extracted from the urine of a 3-year-old patient was investigated by Orbitrap MS equipped with Nanospray Flex Ion Source in the negative ion mode. For structural characterization of several molecular species, collision-induced dissociation MS -MS was carried out using collision energy values within 20-60 eV range. By our approach, 39 novel species associated to this condition were identified, among which O-glycopeptides, free O-glycans and one structure corresponding to an N-glycan never characterized in the context of Schindler disease. The experiments conducted at a resolution of 60 000 allowed the discrimination and identification of a total number of 69 different species with an average mass accuracy of 9.87 ppm, an in-run reproducibility of almost 100%, an experiment-to-experiment and day-to-day reproducibility of about 95%. This study brings contributions in the diagnosis of Schindler disease through the elucidation of potential biomarker species in urine. Our multistage MS results completed with 39 new glycoforms the inventory of potential biomarker structures associated to Schindler disease. For the first time, an N-glycan was identified and structurally characterized in Schindler patient urine, which opens new research directions in the field. Copyright © 2015 John Wiley & Sons, Ltd.

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Section: Resultssupporting

confidence: 88%

Section: Resultsmentioning

confidence: 56%

Section: Introductionmentioning

confidence: 99%

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Identification and structural characterization of novel O‐ and N‐glycoforms in the urine of a Schindler disease patient by Orbitrap mass spectrometry

et al. 2015

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“…Mass spectrometry in direct combination with high‐performance separation techniques or microfluidics has revealed in the last decade the ability to discover in Schindler disease patient urine O ‐glycosylated amino acids and O ‐glycopeptides as potential markers useful for a rapid diagnosis …”

Section: Resultsmentioning

confidence: 99%

“…Several reports on the investigation of Schindler disease glycourinome in the case of two male siblings diagnosed with this condition using advanced mass spectrometry (MS) methods were published in recent years . In some instances, the analysis of the glycopeptides from patient urine was also conducted in comparison with an age‐matched healthy control.…”

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confidence: 99%

Application of ion mobility tandem mass spectrometry to compositional and structural analysis of glycopeptides extracted from the urine of a patient diagnosed with Schindler disease

Sârbu

Zhu

Peter‐Katalinić

et al. 2015

Rapid Comm Mass Spectrometry

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Microfluidics-Mass Spectrometry of Protein-Carbohydrate Interactions: Applications to the Development of Therapeutics and Biomarker Discovery

Zamfir

2017

Methods in Molecular Biology

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The functional interactions of carbohydrates and their protein receptors are the basis of biological events critical to the evolution of pathological states. Hence, for the past years, such interactions have become the focus of research for the development of therapeutics and discovery of novel glycan biomarkers based on their binding affinity. Due to the high sensitivity, throughput, reproducibility, and capability to ionize minor species in heterogeneous mixtures, microfluidics-mass spectrometry (MS) has recently emerged as a method of choice in protein-glycan interactomics. In this chapter, a straightforward microfluidics-based MS methodology for the assessment of protein-glycan interactions is presented. The general protocol encompasses: (1) submission of the interacting partners to a binding assay under conditions mimicking the in vivo environment; and (2) screening of the reaction products and their structural characterization by fully automated chip-nanoelectrospray (nanoESI) MS and multistage MS. The first section of the chapter is devoted to describing a method that enables the study of protein-oligosaccharide interactions by chip-nanoESI quadrupole time-of-flight (QTOF) MS and top-down complex analysis by collision-induced dissociation (CID). This section provides the protocol for the determination of the complex formed by standard β-lactoglobulin (BLG) with maltohexaose (Glc) and recommends as a concrete application the study of the interaction between BLG extracted from human milk with Glc, considered a ligand able to reduce the allergenicity of this protein. The second part is dedicated to presenting the protocols for the binding assay followed by chip-nanoESI ion trap (ITMS) and electron transfer dissociation (ETD) in combination with CID for protein-ganglioside interactions, using as an example the B subunit of cholera toxin (Ctb5) in interaction with comercially available GM1 species. The methodology described may be successfully applied to native ganglioside mixtures from human brain, in particular for discovery of biomarkers on the basis of their binding affinity.

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Automated chip-nanoelectrospray mass spectrometry for glycourinomics in Schindler disease type I

Cited by 8 publications

References 58 publications

Identification and structural characterization of novel O‐ and N‐glycoforms in the urine of a Schindler disease patient by Orbitrap mass spectrometry

Identification and structural characterization of novel O‐ and N‐glycoforms in the urine of a Schindler disease patient by Orbitrap mass spectrometry

Application of ion mobility tandem mass spectrometry to compositional and structural analysis of glycopeptides extracted from the urine of a patient diagnosed with Schindler disease

Microfluidics-Mass Spectrometry of Protein-Carbohydrate Interactions: Applications to the Development of Therapeutics and Biomarker Discovery

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