Dataset Information

LC-MS/MS characterization of xyloside-primed glycosaminoglycans with cell-specific cytotoxic properties reveals structural diversity and novel glycan modifications

ABSTRACT: Structural characterization of glycosaminoglycans remains a challenge and is essential for determining not only structure-function relationships between glycosaminoglycans and the biomolecules with which they interact, but also to gain insight into the biosynthesis of glycosaminoglycans. We have recently reported cytotoxic effects of xyloside-primed chondroitin/dermatan sulfate derived from a human breast carcinoma cell line, HCC70, and shown that it differs in disaccharide composition from non-toxic chondroitin/dermatan sulfate derived from a human breast fibroblast cell line, CCD-1095Sk. To further investigate the structural requirements for the cytotoxic effect, we have here developed a novel LC-MS/MS approach based on dibutylamine ion-pairing reversed-phase chromatography and negative mode higher-energy collision dissociation (HCD), and used it in combination with cell growth studies and disaccharide fingerprinting. This allowed for detailed structural characterization of linkage regions, internal oligosaccharides, and non-reducing ends, showing not only differences between xyloside-primed chondroitin/dermatan sulfate from HCC70 cells and CCD-1095Sk cells, but also in sialylation of the linkage region as well as previously undescribed methylation and sulfation of the non-reducing ends. Although the xyloside-primed chondroitin/dermatan sulfate from HCC70 cells was less complex in terms of presence and distribution of iduronic acid than that from CCD-1095Sk cells, both glucuronic acid and iduronic acid appeared essential for the cytotoxic effect. Our data have moved us one step closer to understanding the structure of the cytotoxic chondroitin/dermatan sulfate from HCC70 cells primed on xylosides, and demonstrate the suitability of the LC-MS/MS approach for structural characterization of glycosaminoglycans.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Fibroblast

DISEASE(S): Breast Cancer

SUBMITTER: Egor Vorontsov

LAB HEAD: Göran Larson

PROVIDER: PXD009652 | Pride | 2018-05-07

REPOSITORIES: Pride

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Publications

LC-MS/MS characterization of xyloside-primed glycosaminoglycans with cytotoxic properties reveals structural diversity and novel glycan modifications.

Persson Andrea A Gomez Toledo Alejandro A Vorontsov Egor E Nasir Waqas W Willén Daniel D Noborn Fredrik F Ellervik Ulf U Mani Katrin K Nilsson Jonas J Larson Göran G

The Journal of biological chemistry 20180508 26

Structural characterization of glycosaminoglycans remains a challenge but is essential for determining structure-function relationships between glycosaminoglycans and the biomolecules with which they interact and for gaining insight into the biosynthesis of glycosaminoglycans. We have recently reported that xyloside-primed chondroitin/dermatan sulfate derived from a human breast carcinoma cell line, HCC70, has cytotoxic effects and shown that it differs in disaccharide composition from nontoxic ...[more]

PMID: 29739851

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Dataset Information

LC-MS/MS characterization of xyloside-primed glycosaminoglycans with cell-specific cytotoxic properties reveals structural diversity and novel glycan modifications

Publications

LC-MS/MS characterization of xyloside-primed glycosaminoglycans with cytotoxic properties reveals structural diversity and novel glycan modifications.

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