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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Published inAnalytical chemistry (Washington) Vol. 84; no. 13; pp. 5475 - 5478
Main Authors Kailemia, Muchena J, Li, Lingyun, Ly, Mellisa, Linhardt, Robert J, Amster, I. Jonathan
Format Journal Article
LanguageEnglish
Published Washington, DC American Chemical Society 03.07.2012
Subjects
Analytical chemistry
Anticoagulants - chemistry
Chemistry
Exact sciences and technology
Fondaparinux
Heparin, Low-Molecular-Weight - chemistry
Hydrogen - chemistry
Ions
Ions - chemistry
Mass spectrometry
Molecules
Polysaccharides - chemistry
Prescription drugs
Sodium - chemistry
Spectrometric and optical methods
Sulfates - chemistry
Tandem Mass Spectrometry - methods
Drug
Time
Characterization
Molecules
Target
Residue
Mass spectrometry MS/MS
Uronic acid
Glycosaminoglycan
Dissociation
Heparin
Molecular mass
Structural analysis
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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.
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ISSN:0003-2700
1520-6882
DOI:10.1021/ac3015824