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Sialylation analysis of O-glycosylated sialylated peptides from urine of patients suffering from Schindler's disease by Fourier transform ion cyclotron resonance mass spectrometry and sustained off-resonance irradiation collision-induced dissociation.
- Source :
-
Rapid communications in mass spectrometry : RCM [Rapid Commun Mass Spectrom] 2003; Vol. 17 (24), pp. 2822-32. - Publication Year :
- 2003
-
Abstract
- A strategy based on Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) for screening of complex glycoconjugate mixtures containing O-linked glycopeptides and O-glycosylated amino acids with alpha-N-acetylgalactosaminyl residues is presented. To detect and identify O-glycoforms present in urine of patients suffering from hereditary N-acetylhexosaminidase deficiency (known as Schindler's disease), present at 100 times higher concentrations than in urine of healthy controls, new accurate methods for mapping and sequencing were required. In the mass spectrometric analysis particular attention has to be paid to original sialylation patterns, because of the potential lability of the sialic acid moiety during the desorption/ionization process. Negative ion nanoelectrospray ionization (nanoESI) FTICR-MS at 9.4 T is shown here to represent a method of choice for identification of single components in such complex glycomixtures due to high resolution and mass accuracy. By optimization of sustained off-resonance irradiation collision-induced dissociation tandem mass spectrometry (SORI-CID-MS(2)) in the negative ion mode, the type and sequence of the sialylated glycopeptide components were determined from their fragmentation patterns. Additionally, implementation of SORI-CID-MS(3) provides detailed information for sialylation analysis. The potential diagnostic value of this approach is discussed.<br /> (Copyright 2003 John Wiley & Sons, Ltd.)
- Subjects :
- Cyclotrons
Glycosylation
Humans
Indicators and Reagents chemistry
Peptides chemistry
Peptides urine
Reproducibility of Results
Sensitivity and Specificity
Spectrometry, Mass, Electrospray Ionization methods
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization methods
Spectroscopy, Fourier Transform Infrared
beta-N-Acetylhexosaminidases chemistry
Brain Diseases, Metabolic, Inborn urine
Mass Spectrometry methods
N-Acetylneuraminic Acid chemistry
Urinalysis methods
beta-N-Acetylhexosaminidases deficiency
beta-N-Acetylhexosaminidases urine
Subjects
Details
- Language :
- English
- ISSN :
- 0951-4198
- Volume :
- 17
- Issue :
- 24
- Database :
- MEDLINE
- Journal :
- Rapid communications in mass spectrometry : RCM
- Publication Type :
- Academic Journal
- Accession number :
- 14673833
- Full Text :
- https://doi.org/10.1002/rcm.1273