Complete mass spectral characterization of a synthetic ultralow molecular weight heparin using collision induced dissociation

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Authors
Kailemia, Muchena J.
Li, Lingyun
Ly, Mellisa
Linhardt, Robert J.
Amster, I. Jonathan
Issue Date
2012-07-03
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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Abstract
Glycosaminoglycans (GAGs) are a class of biologically important molecules, and their structural analysis is the target of considerable research effort. Advances in tandem mass spectrometry (MS/MS) have recently enabled the structural characterization of several classes of GAGs; however, the highly sulfated GAGs, such as heparins, have remained a relatively intractable class due their tendency to lose SO3 during MS/MS, producing few sequence-informative fragment ions. The present work demonstrates for the first time the complete structural characterization of the highly sulfated heparin-based drug Arixtra. This was achieved by Na+/H+ exchange to create a more ionized species that was stable against SO3 loss, and that produced complete sets of both glycosidic and cross-ring fragment ions. MS/MS enables the complete structural determination of Arixtra, including the stereochemistry of its uronic acid residues, and suggests an approach for solving the structure of more complex, highly sulfated heparin-based drugs.
Description
Analytical Chemistry, 84, 5475-5478
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Full Citation
Complete mass spectral characterization of a synthetic ultralow molecular weight heparin using collision induced dissociation, M. J. Kailemia, L. Li, M. Ly, R. J. Linhardt, J. Amster, Analytical Chemistry, 84, 5475-5478, 2012.
Publisher
American Chemical Society (ACS)
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Volume
Issue
PubMed ID
DOI
ISSN
15206882
32700
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