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 sulfated GAGs, such as heparins, have remained a relatively intractable class due their tendency to lose SO(3) 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 SO(3) 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.
Muchena J
MJ
Kailemia
Lingyun
L
Li
Mellisa
M
Ly
Robert J
RJ
Linhardt
I Jonathan
IJ
Amster
D000925:Anticoagulants / Q000737:chemistry*; D000077425:Fondaparinux; D006495:Heparin, Low-Molecular-Weight / Q000737:chemistry*; D006859:Hydrogen / Q000737:chemistry; D007477:Ions / Q000737:chemistry; D011134:Polysaccharides / Q000737:chemistry*; D012964:Sodium / Q000737:chemistry; D013431:Sulfates / Q000737:chemistry; D053719:Tandem Mass Spectrometry / Q000379:methods*
D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D007477:Ions; D011134:Polysaccharides; D013431:Sulfates; D006859:Hydrogen; D012964:Sodium; D000077425:Fondaparinux