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Application of ion mobility tandem mass spectrometry to compositional and structural analysis of glycopeptides extracted from the urine of a patient diagnosed with Schindler disease
Author(s) -
Sarbu Mirela,
Zhu Feifei,
PeterKatalinić Jasna,
Clemmer David E.,
Zamfir Alina D.
Publication year - 2015
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.7288
Subject(s) - chemistry , tandem mass spectrometry , mass spectrometry , chromatography , ion mobility spectrometry , glycopeptide , electrospray ionization , collision induced dissociation , selected reaction monitoring , analytical chemistry (journal) , biochemistry , antibiotics
Rationale Schindler disease is caused by the deficient activity of α‐ N ‐acetylgalactosaminidase, which leads to an abnormal accumulation of O ‐glycopeptides in tissues and body fluids. In this work the Schindler condition is for the first time approached by ion mobility (IMS) tandem mass spectrometry (MS/MS), for determining urine glycopeptide fingerprints and discriminate isomeric structures. Methods IMS‐MS experiments were conducted on a Synapt G2s mass spectrometer operating in negative ion mode. A glycopeptide mixture extracted from the urine of a patient suffering from Schindler disease was dissolved in methanol and infused into the mass spectrometer by electrospray ionization using a syringe‐pump system. MS/MS was performed by collision‐induced dissociation (CID) at low energies, after mobility separation in the transfer cell. Data acquisition and processing were performed using MassLynx and Waters Driftscope software. Results IMS‐MS data indicated that the attachment of one or two amino acids to the carbohydrate backbone has a minimal influence on the molecule conformation, which limits the discrimination of the free oligosaccharides from the glycosylated amino acids and dipeptides. The structural analysis by CID MS/MS in combination with IMS‐MS of species exhibiting the same m/z but different configurations demonstrated for the first time the presence of positional isomers for some of the Schindler disease biomarker candidates. Conclusions The IMS‐MS and CID MS/MS platform was for the first time optimized and applied to Schindler disease glycourinome. By this approach the separation and characterization of Neu5Ac positional isomers was possible. IMS CID MS/MS showed the ability to determine the type of the glycopeptide isomers from a series of possible candidates. Copyright © 2015 John Wiley & Sons, Ltd.