Cargando…

Ion Mobility Mass Spectrometry Reveals Rare Sialylated Glycosphingolipid Structures in Human Cerebrospinal Fluid

Gangliosides (GGs) represent an important class of biomolecules associated with the central nervous system (CNS). In view of their special role at a CNS level, GGs are valuable diagnostic markers and prospective therapeutic agents. By ion mobility separation mass spectrometry (IMS MS), recently impl...

Descripción completa

Detalles Bibliográficos
Autores principales: Sarbu, Mirela, Fabris, Dragana, Vukelić, Željka, Clemmer, David E., Zamfir, Alina D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8839488/
https://www.ncbi.nlm.nih.gov/pubmed/35164008
http://dx.doi.org/10.3390/molecules27030743
_version_ 1784650381726318592
author Sarbu, Mirela
Fabris, Dragana
Vukelić, Željka
Clemmer, David E.
Zamfir, Alina D.
author_facet Sarbu, Mirela
Fabris, Dragana
Vukelić, Željka
Clemmer, David E.
Zamfir, Alina D.
author_sort Sarbu, Mirela
collection PubMed
description Gangliosides (GGs) represent an important class of biomolecules associated with the central nervous system (CNS). In view of their special role at a CNS level, GGs are valuable diagnostic markers and prospective therapeutic agents. By ion mobility separation mass spectrometry (IMS MS), recently implemented by us in the investigation of human CNS gangliosidome, we previously discovered a similarity between GG profiles in CSF and the brain. Based on these findings, we developed IMS tandem MS (MS/MS) to characterize rare human CSF glycoforms, with a potential biomarker role. To investigate the oligosaccharide and ceramide structures, the ions detected following IMS MS separation were submitted to structural analysis by collision-induced dissociation (CID) MS/MS in the transfer cell. The IMS evidence on only one mobility feature, together with the diagnostic fragment ions, allowed the unequivocal identification of isomers in the CSF. Hence, by IMS MS/MS, GalNAc-GD1c(d18:1/18:1) and GalNAc-GD1c(d18:1/18:0) having both Neu5Ac residues and GalNAc attached to the external galactose were for the first time discovered and structurally characterized. The present results demonstrate the high potential of IMS MS/MS for biomarker discovery and characterization in body fluids, and the perspectives of method implementation in clinical analyses targeting the early diagnosis of CNS diseases through molecular fingerprints.
format Online
Article
Text
id pubmed-8839488
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-88394882022-02-13 Ion Mobility Mass Spectrometry Reveals Rare Sialylated Glycosphingolipid Structures in Human Cerebrospinal Fluid Sarbu, Mirela Fabris, Dragana Vukelić, Željka Clemmer, David E. Zamfir, Alina D. Molecules Article Gangliosides (GGs) represent an important class of biomolecules associated with the central nervous system (CNS). In view of their special role at a CNS level, GGs are valuable diagnostic markers and prospective therapeutic agents. By ion mobility separation mass spectrometry (IMS MS), recently implemented by us in the investigation of human CNS gangliosidome, we previously discovered a similarity between GG profiles in CSF and the brain. Based on these findings, we developed IMS tandem MS (MS/MS) to characterize rare human CSF glycoforms, with a potential biomarker role. To investigate the oligosaccharide and ceramide structures, the ions detected following IMS MS separation were submitted to structural analysis by collision-induced dissociation (CID) MS/MS in the transfer cell. The IMS evidence on only one mobility feature, together with the diagnostic fragment ions, allowed the unequivocal identification of isomers in the CSF. Hence, by IMS MS/MS, GalNAc-GD1c(d18:1/18:1) and GalNAc-GD1c(d18:1/18:0) having both Neu5Ac residues and GalNAc attached to the external galactose were for the first time discovered and structurally characterized. The present results demonstrate the high potential of IMS MS/MS for biomarker discovery and characterization in body fluids, and the perspectives of method implementation in clinical analyses targeting the early diagnosis of CNS diseases through molecular fingerprints. MDPI 2022-01-24 /pmc/articles/PMC8839488/ /pubmed/35164008 http://dx.doi.org/10.3390/molecules27030743 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sarbu, Mirela
Fabris, Dragana
Vukelić, Željka
Clemmer, David E.
Zamfir, Alina D.
Ion Mobility Mass Spectrometry Reveals Rare Sialylated Glycosphingolipid Structures in Human Cerebrospinal Fluid
title Ion Mobility Mass Spectrometry Reveals Rare Sialylated Glycosphingolipid Structures in Human Cerebrospinal Fluid
title_full Ion Mobility Mass Spectrometry Reveals Rare Sialylated Glycosphingolipid Structures in Human Cerebrospinal Fluid
title_fullStr Ion Mobility Mass Spectrometry Reveals Rare Sialylated Glycosphingolipid Structures in Human Cerebrospinal Fluid
title_full_unstemmed Ion Mobility Mass Spectrometry Reveals Rare Sialylated Glycosphingolipid Structures in Human Cerebrospinal Fluid
title_short Ion Mobility Mass Spectrometry Reveals Rare Sialylated Glycosphingolipid Structures in Human Cerebrospinal Fluid
title_sort ion mobility mass spectrometry reveals rare sialylated glycosphingolipid structures in human cerebrospinal fluid
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8839488/
https://www.ncbi.nlm.nih.gov/pubmed/35164008
http://dx.doi.org/10.3390/molecules27030743
work_keys_str_mv AT sarbumirela ionmobilitymassspectrometryrevealsraresialylatedglycosphingolipidstructuresinhumancerebrospinalfluid
AT fabrisdragana ionmobilitymassspectrometryrevealsraresialylatedglycosphingolipidstructuresinhumancerebrospinalfluid
AT vukeliczeljka ionmobilitymassspectrometryrevealsraresialylatedglycosphingolipidstructuresinhumancerebrospinalfluid
AT clemmerdavide ionmobilitymassspectrometryrevealsraresialylatedglycosphingolipidstructuresinhumancerebrospinalfluid
AT zamfiralinad ionmobilitymassspectrometryrevealsraresialylatedglycosphingolipidstructuresinhumancerebrospinalfluid