Multistage tandem mass spectrometry of chondroitin sulfate and dermatan sulfate

Chondroitin/dermatan sulfate (CS/DS) is a glycosaminoglycan (GAG) found in abundance in extracellular matrices. In connective tissue, CS/DS proteoglycans play structural roles in maintaining viscoelasticity through the large number of immobilized sulfate groups on CS/DS chains. CS/DS chains also bind protein families including growth factors and growth factor receptors. Through such interactions, CS/DS chains play important roles in neurobiochemical processes, connective tissue homeostasis, coagulation, and cell growth regulation. Expression of DS has been observed to increase in cancerous tissue relative to controls. In earlier studies, MS2 was used to compare the types of CS/DS isomers present in biological samples. The results demonstrated that product ion abundances reflect the types of CS/DS repeats present and can be used quantitatively. It was not clear, however, to which of the CS/DS repeats the product ions abundances were sensitive. The present work explores the utility of MS3 for structural characterization of CS/DS oligosaccharides. The data show that MS3 product ion abundances correlate with the presence of DS-like repeats in specific positions on the oligosaccharide chains.

Graphical abstractFigure optionsDownload full-size imageDownload high-quality image (104 K)Download as PowerPoint slideResearch highlights▶ Multistage tandem MS of chondroitin sulfate. ▶ Diagnostic product ions for chondroitin sulfate classes. ▶ Gas phase decomposition of chondroitin sulfate.