TY - JOUR
T1 - Electron detachment dissociation and infrared multiphoton dissociation of heparin tetrasaccharides
AU - Leach, Franklin E.
AU - Xiao, Zhongping
AU - Laremore, Tatiana N.
AU - Linhardt, Robert J.
AU - Amster, I. Jonathan
N1 - Funding Information:
The authors would like to acknowledge Professor John Eyler for his contributions to FTMS, tandem mass spectrometry, and the structural analysis of carbohydrates. The authors gratefully acknowledge financial support from the National Institutes of Health grant # 2R01-GM038060-16 . FEL III personally acknowledges the University of Georgia Graduate School for funding from a Dissertation Completion Award.
PY - 2011/12/1
Y1 - 2011/12/1
N2 - Heparin glycosaminoglycans (GAGs) present the most difficult glycoform for analytical characterization due to high levels of sulfation and structural heterogeneity. Recent contamination of the clinical heparin supply and subsequent fatalities has highlighted the need for sensitive methodologies of analysis. In the last decade, tandem mass spectrometry has been increasingly applied for the analysis of GAGs, but developments in the characterization of highly sulfated compounds have been minimal due to the low number of cross-ring cleavages generated by threshold ion activation by collisional induced dissociation (CID). In the current work, electron detachment dissociation (EDD) and infrared multiphoton dissociation (IRMPD) are applied to a series of heparin tetrasaccharides. With both activation methods, abundant glycosidic and cross-ring cleavages are observed. The concept of Ionized Sulfate Criteria (ISC) is presented as a succinct method for describing the charge state, degree of ionization and sodium/proton exchange in the precursor ion. These factors contribute to the propensity for useful fragmentation during MS/MS measurements. Precursors with ISC values of 0 are studied here, and shown to yield adequate structural information from ion activation by EDD or IRMPD.
AB - Heparin glycosaminoglycans (GAGs) present the most difficult glycoform for analytical characterization due to high levels of sulfation and structural heterogeneity. Recent contamination of the clinical heparin supply and subsequent fatalities has highlighted the need for sensitive methodologies of analysis. In the last decade, tandem mass spectrometry has been increasingly applied for the analysis of GAGs, but developments in the characterization of highly sulfated compounds have been minimal due to the low number of cross-ring cleavages generated by threshold ion activation by collisional induced dissociation (CID). In the current work, electron detachment dissociation (EDD) and infrared multiphoton dissociation (IRMPD) are applied to a series of heparin tetrasaccharides. With both activation methods, abundant glycosidic and cross-ring cleavages are observed. The concept of Ionized Sulfate Criteria (ISC) is presented as a succinct method for describing the charge state, degree of ionization and sodium/proton exchange in the precursor ion. These factors contribute to the propensity for useful fragmentation during MS/MS measurements. Precursors with ISC values of 0 are studied here, and shown to yield adequate structural information from ion activation by EDD or IRMPD.
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U2 - 10.1016/j.ijms.2011.08.029
DO - 10.1016/j.ijms.2011.08.029
M3 - Article
C2 - 22247649
AN - SCOPUS:80955166248
SN - 1387-3806
VL - 308
SP - 253
EP - 259
JO - International Journal of Mass Spectrometry
JF - International Journal of Mass Spectrometry
IS - 2-3
ER -