Complete Mass Spectral Characterization of a Synthetic Ultralow-Molecular-Weight Heparin Using Collision-Induced Dissociation

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 s...

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Bibliographic Details
Published in:Analytical chemistry (Washington) 2012-07, Vol.84 (13), p.5475-5478
Main Authors: Kailemia, Muchena J, Li, Lingyun, Ly, Mellisa, Linhardt, Robert J, Amster, I. Jonathan
Format: Article
Language:English
Subjects:
Analytical chemistry
Anticoagulants - chemistry
Chemistry
drugs
Exact sciences and technology
Fondaparinux
heparin
Heparin, Low-Molecular-Weight - chemistry
Hydrogen - chemistry
ionization
Ions
Ions - chemistry
Mass spectrometry
Molecules
Polysaccharides - chemistry
Prescription drugs
protons
sodium
Sodium - chemistry
Spectrometric and optical methods
stereochemistry
Sulfates - chemistry
tandem mass spectrometry
Tandem Mass Spectrometry - methods
uronic acids
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Summary: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.
ISSN:0003-2700
1520-6882
1520-6882
DOI:10.1021/ac3015824