| Autor: |
Sarbu M; Department of Condensed Matter, National Institute for Research and Development in Electrochemistry and Condensed Matter, Timisoara 300224, Romania., Seidler DG; SYNLAB Holding Deutschland GmbH, Trier 54290, Germany., Clemmer DE; Department of Chemistry, The College of Arts & Science, Indiana University, Bloomington, Indiana 47405, United States., Zamfir AD; Department of Condensed Matter, National Institute for Research and Development in Electrochemistry and Condensed Matter, Timisoara 300224, Romania.; Department of Technical and Natural Sciences, 'Aurel Vlaicu' University of Arad, Arad 310330, Romania. |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of the American Society for Mass Spectrometry [J Am Soc Mass Spectrom] 2024 Sep 04; Vol. 35 (9), pp. 2102-2117. Date of Electronic Publication: 2024 Aug 23. |
| DOI: |
10.1021/jasms.4c00159 |
| Abstrakt: |
Glycosaminoglycans (GAGs) are sulfated linear O -glycan chains abundantly expressed in the extracellular matrix (ECM). Among GAGs, chondroitin sulfate (CS) and dermatan sulfate (DS) play important roles at the brain level, where the distribution and location of the sulfates within the CS/DS chains are responsible for numerous biological events. The diversity of the neural hybrid CS/DS expressed in the brain and the need to elucidate their structure gave rise to considerable efforts toward the development of analytical methods able to discover novel regularly and irregularly sulfated domains. In this context, we report here the introduction of ion mobility separation (IMS) mass spectrometry (MS) in brain glycosaminoglycomics. Based on IMS MS and tandem MS (MS/MS) by collision-induced dissociation (CID), we have developed a powerful approach for the screening and structural analysis of neural CS/DS and optimized and validated the method for the structural analysis of octasaccharides that were released from brain proteoglycans by β-elimination and pooled after chain depolymerization using chondroitin AC lyase. The IMS MS data revealed the separation of CS/DS octamers into mobility families based on the amount of sulfation. Among the discovered oversulfated domains, of major biological importance is the pentasulfated-[4,5-Δ-GlcAGalNAc(IdoAGalNAc) 3 ], for which the (-) nanoESI IMS CID MS/MS analysis disclosed through the presence of distinct drift times, the incidence of two isomers. Moreover, the generated fragment ions revealed an uncommon trisulfated motif and an uncommon pentasulfated motif. Hence, using IMS MS and CID MS/MS, novel brain-related CS/DS domains of atypical sulfation patterns were discovered and structurally characterized in detail. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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