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Identification of a non-canonical chondroitin sulfate linkage region trisaccharide

Journal article
Authors Andrea Persson
Jonas Nilsson
Egor Vorontsov
Fredrik Noborn
Göran Larson
Published in Glycobiology
Volume 29
Issue 5
Pages 366-371
ISSN 0959-6658
Publication year 2019
Published at Core Facilities, Proteomics
Institute of Medicine
Pages 366-371
Language en
Links dx.doi.org/10.1093/glycob/cwz014
Subject categories Biochemistry and Molecular Biology, Cell and molecular biology

Abstract

It is generally accepted that the biosynthesis of chondroitin sulfate and heparan sulfate is proceeding from a common linkage region tetrasaccharide comprising GlcA-Gal-Gal-Xyl-O-. The linkage region can undergo various modifications such as sulfation, phosphorylation and sialylation, and as the methods for studying glycosaminoglycan structure have been developed and refined, the number of discovered modifications has increased. Previous studies on the linkage region and the glycosyltransferases involved in the biosynthesis suggest that variants of the linkage region tetrasaccharide may also be possible. Here, using LC-MS/MS, we describe a non-canonical linkage region trisaccharide comprising GlcA-Gal-Xyl-O-. The trisaccharide was identified as a minor constituent in the proteoglycan bikunin from urine of human healthy donors present as a disulfated pentasaccharide, Delta HexA-GalNAc(S)-GlcA-Gal(S)-Xyl-O-, after chondroitinase ABC degradation. Furthermore, it was present as the corresponding disulfated pentasaccharide after chondroitinase ABC degradation in chondroitin sulfate primed on xylosides isolated from human cell lines. This linkage region trisaccharide may serve as an alternative point of entry for glycosaminoglycan biosynthesis.

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