title: Heparin characterization: challenges and solutions.
abstract: Although heparin is an important and widely prescribed pharmaceutical anticoagulant, its high degree of sequence microheterogeneity and size polydispersity make molecular-level characterization challenging. Unlike nucleic acids and proteins that are biosynthesized through template-driven assembly processes, heparin and the related glycosaminoglycan heparan sulfate are actively remodeled during biosynthesis through a series of enzymatic reactions that lead to variable levels of O- and N-sulfonation and uronic acid epimers. As summarized in this review, heparin sequence information is determined through a bottom-up approach that relies on depolymerization reactions, size- and charge-based separations, and sensitive mass spectrometric and nuclear magnetic resonance experiments to determine the structural identity of component oligosaccharides. The structure-elucidation process, along with its challenges and opportunities for future analytical improvements, is reviewed and illustrated for a heparin-derived hexasaccharide.
authors.affiliation: Department of Chemistry, University of California, Riverside, California 92521, USA. cjone004@ucr.edu
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Jones
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Beni
authors.forename: John F K
authors.initials: JF
authors.lastname: Limtiaco
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Langeslay
authors.forename: Cynthia K
authors.initials: CK
authors.lastname: Larive
mesh_terms: D002240:Carbohydrate Sequence; D006493:Heparin / Q000737:chemistry*; D013058:Mass Spectrometry; D008969:Molecular Sequence Data
chemical_list: D006493:Heparin