Domain Mapping of Chondroitin/Dermatan Sulfate Glycosaminoglycans Enables Structural Characterization of Proteoglycans

Persson, Andrea; Nikpour, Mahnaz; Vorontsov, Egor; Nilsson, Jonas; Larson, Göran

doi:10.1016/j.mcpro.2021.100074

Cited by 12 publications

(11 citation statements)

References 46 publications

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“…The development of a number of mAbs to specific CS sulfation motifs has facilitated the mapping of these motifs along CS and DS chains [ 13 , 79 , 80 , 81 ]. Mapping of CS/DS GAG domains has also enabled the structural characterization of PGs [ 81 , 82 , 83 ]. A HS Interactome study documents a large number of HS interactive ligands [ 17 ].…”

Section: The Cell Instructive Properties Of Gagsmentioning

confidence: 99%

HS, an Ancient Molecular Recognition and Information Storage Glycosaminoglycan, Equips HS-Proteoglycans with Diverse Matrix and Cell-Interactive Properties Operative in Tissue Development and Tissue Function in Health and Disease

Hayes

Melrose

2023

IJMS

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Heparan sulfate is a ubiquitous, variably sulfated interactive glycosaminoglycan that consists of repeating disaccharides of glucuronic acid and glucosamine that are subject to a number of modifications (acetylation, de-acetylation, epimerization, sulfation). Variable heparan sulfate chain lengths and sequences within the heparan sulfate chains provide structural diversity generating interactive oligosaccharide binding motifs with a diverse range of extracellular ligands and cellular receptors providing instructional cues over cellular behaviour and tissue homeostasis through the regulation of essential physiological processes in development, health, and disease. heparan sulfate and heparan sulfate-PGs are integral components of the specialized glycocalyx surrounding cells. Heparan sulfate is the most heterogeneous glycosaminoglycan, in terms of its sequence and biosynthetic modifications making it a difficult molecule to fully characterize, multiple ligands also make an elucidation of heparan sulfate functional properties complicated. Spatio-temporal presentation of heparan sulfate sulfate groups is an important functional determinant in tissue development and in cellular control of wound healing and extracellular remodelling in pathological tissues. The regulatory properties of heparan sulfate are mediated via interactions with chemokines, chemokine receptors, growth factors and morphogens in cell proliferation, differentiation, development, tissue remodelling, wound healing, immune regulation, inflammation, and tumour development. A greater understanding of these HS interactive processes will improve therapeutic procedures and prognoses. Advances in glycosaminoglycan synthesis and sequencing, computational analytical carbohydrate algorithms and advanced software for the evaluation of molecular docking of heparan sulfate with its molecular partners are now available. These advanced analytic techniques and artificial intelligence offer predictive capability in the elucidation of heparan sulfate conformational effects on heparan sulfate-ligand interactions significantly aiding heparan sulfate therapeutics development.

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Section: The Cell Instructive Properties Of Gagsmentioning

confidence: 99%

HS, an Ancient Molecular Recognition and Information Storage Glycosaminoglycan, Equips HS-Proteoglycans with Diverse Matrix and Cell-Interactive Properties Operative in Tissue Development and Tissue Function in Health and Disease

Hayes

Melrose

2023

IJMS

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“…HexNAc or a HexN with 0-2 sulfate groups bound at various positions, as well as saturated GAG-NRE saccharides (from the terminal non-reducing end of the GAG chains) (Fig. 1a) [23,24].…”

Section: Release and Analysis Of Hs-and Cs In Urinementioning

confidence: 99%

“…We recently introduced the GAG domain mapping (GAGDoMa) approach where the GAG-NRE, internal saccharide and linkage region domain, obtained after bacterial lyase depolymerizations of cellular CS/DS GAGs, are analyzed by nano-ow LC-MS/MS to provide a three-part domain structural analysis of the CS/DS GAG chains [23,24]. Here, we applied our GAGDoMa approach to develop a straightforward glycomic work ow for the clinical laboratory for the accurate subtyping of MPS disorders.…”

Section: Mps Subgroupmentioning

confidence: 99%

A glycomic workflow for LC-MS/MS analysis of urine glycosaminoglycan biomarkers in mucopolysaccharidoses

Nilsson

Persson

Voronstov

et al. 2023

Preprint

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In recent years, several rational designed therapies have been developed for treatment of mucopolysaccharidoses (MPS), a group of inherited metabolic disorders in which glycosaminoglycans (GAGs) are accumulated in various tissues and organs. Thus, improved disease-specific biomarkers for diagnosis and monitoring treatment efficacy are of paramount importance. Specific non-reducing end GAG structures (GAG-NREs) have become promising biomarkers for MPS, as the compositions of the GAG-NREs depend on the nature of the lysosomal enzyme deficiency, thereby creating a specific pattern for each subgroup. However, there is yet no straightforward clinical laboratory platform which can assay all MPS-related GAG-NREs in one single analysis. Here, we developed and applied a GAG domain mapping approach for analyses of urine samples of ten MPS patients with various MPS diagnoses and corresponding aged-matched controls. We describe a nano-LC-MS/MS method of GAG-NRE profiling, utilizing 2-aminobenzamide reductive amination labeling to improve the sensitivity and the chromatographic resolution. Diagnostic urinary GAG-NREs were identified for MPS types IH/IS, II, IIIc, IVa and VI, corroborating GAG-NRE as biomarkers for these known enzyme deficiencies. Furthermore, a significant reduction of diagnostic urinary GAG-NREs in MPS IH (n = 2) and MPS VI (n = 1) patients under treatment was demonstrated. We argue that this straightforward glycomic workflow, designed for the clinical analysis of MPS-related GAG-NREs in one single analysis, will be of value for expanding the use of GAG-NREs as biomarkers for MPS diagnosis and treatment monitoring.

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“…Therefore, several efficient separation techniques, including capillary electrophoresis (CE) and high-performance liquid chromatography (HPLC), 49,[52][53][54][55][56][57][58][59][60][61] as well as tandem MS (MS/MS), based on collisioninduced dissociation (CID) 47,54,[62][63][64][65] or electron detachment dissociation (EDD), and automated peak detection were combined with ESI MS to investigate different aspects related to CS, DS, or hybrid CS/DS and to obtain information on sulfation sites 47,64 and/or epimerization. 49,66,67 Although the abovementioned techniques enhanced a better knowledge on the composition of natural GAGs, they still have several limitations: (a) laborious sample preparation procedures;…”

mentioning

confidence: 99%

Glycomics by ion mobility tandem mass spectrometry of chondroitin sulfate disaccharide domain in biglycan

et al. 2023

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Biglycan (BGN), a small leucine-rich repeat proteoglycan, is involved in a variety of pathological processes including malignant transformation, for which the upregulation of BGN was found related to cancer cell invasiveness. Because the functions of BGN are mediated by its chondroitin/dermatan sulfate (CS/DS) chains through the sulfates, the determination of CS/DS structure and sulfation pattern is of major importance. In this study, we have implemented an advanced glycomics method based on ion mobility separation (IMS) mass spectrometry (MS) and tandem MS (MS/MS) to characterize the CS disaccharide domains in BGN. The high separation efficiency and sensitivity of this technique allowed the discrimination of five distinct CS disaccharide motifs, of which four irregulated in their sulfation pattern. For the first time, trisulfated unsaturated and bisulfated saturated disaccharides were found in BGN, the latter species documenting the non-reducing end of the chains. The structural investigation by IMS MS/MS disclosed that in one or both of the CS/DS chains, the non-reducing end is 3-O-sulfated GlcA in a rather rare bisulfated motif having the structure 3-O-sulfated GlcA-4-O-sulfated GalNAc. Considering the role played by BGN in cancer cell spreading, the influence on this process of the newly identified sequences will be investigated in the future.

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Domain Mapping of Chondroitin/Dermatan Sulfate Glycosaminoglycans Enables Structural Characterization of Proteoglycans

Cited by 12 publications

References 46 publications

HS, an Ancient Molecular Recognition and Information Storage Glycosaminoglycan, Equips HS-Proteoglycans with Diverse Matrix and Cell-Interactive Properties Operative in Tissue Development and Tissue Function in Health and Disease

HS, an Ancient Molecular Recognition and Information Storage Glycosaminoglycan, Equips HS-Proteoglycans with Diverse Matrix and Cell-Interactive Properties Operative in Tissue Development and Tissue Function in Health and Disease

A glycomic workflow for LC-MS/MS analysis of urine glycosaminoglycan biomarkers in mucopolysaccharidoses

Glycomics by ion mobility tandem mass spectrometry of chondroitin sulfate disaccharide domain in biglycan

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