title: Affinity capillary electrophoresis for the determination of binding affinities for low molecular weight heparins and antithrombin-III.
abstract: The anticoagulant properties of heparin stem in part from high-affinity binding to antithrombin-III (AT-III) inducing a 300-fold increase in its inhibitory activity against the coagulation protease factor Xa. The minimal structural requirements for AT-III binding are contained in the rare heparin pentasaccharide sequence containing a 3,6-O-sulfated N-sulfoglucosamine residue. ACE is used in this work to measure the relative AT-III binding affinities of the low molecular weight heparins (LWMHs) dalteparin, enoxaparin, and tinzaparin and the synthetic pentasaccharide drug fondaparinux (Arixtra). Determination of the AT-III binding affinities of the LWMHs is complicated by their inherent structural heterogeneity and polydispersity. The fractional composition of 3-O-sulfo-N-sulfoglucosamine residues was determined for each drug substance using 2D NMR and used in the interpretation of the ACE results.
authors.affiliation: Department of Chemistry, University of California-Riverside, Riverside, CA, USA.
authors.forename: Meredith M
authors.initials: MM
authors.lastname: Dinges
authors.forename: Kemal
authors.initials: K
authors.lastname: Solakyildirim
authors.forename: Cynthia K
authors.initials: CK
authors.lastname: Larive
mesh_terms: D000990:Antithrombin III / Q000378:metabolism*; D019075:Electrophoresis, Capillary / Q000379:methods*; D006495:Heparin, Low-Molecular-Weight / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods
chemical_list: D006495:Heparin, Low-Molecular-Weight; D000990:Antithrombin III
keywords: ACE; Dalteparin; Enoxaparin; Fondaparinux; Tinzaparin