4.5 Article

Antithrombin III-Binding Site Analysis of Low-Molecular-Weight Heparin Fractions

Journal

JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 107, Issue 5, Pages 1290-1295

Publisher

WILEY
DOI: 10.1016/j.xphs.2018.01.008

Keywords

heparin; LMWH; gel permeation chromatography; compositional analysis; LC-MS; SPR

Funding

  1. National Institutes of Health [HL125371, GM10213, HL136271]
  2. Foundation of Zhejiang Province Educational Committee [Y201328477]

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Low-molecular-weight heparins (LMWHs) are widely used as clinical anticoagulant drugs. LMWHs are heterogeneous and highly negatively charged glycans prepared by chemical or enzymatic depolymerization of unfractionated heparin. The detailed structural analysis of a LMWH is essential for the drug quality control. In this study, an LMWH, enoxaparin sodium (a generic version of Lovenox) was separated into different molecular weight fractions by a Superdex peptide column. The disaccharide compositions, 3-O-sulfo groupecontaining tetrasaccharides composition, and antithrombin III-binding affinity of the fractions from this LMWH were analyzed. The results showed that all the fractions had very similar disaccharide and 3-O-sulfo groupecontaining tetrasaccharide compositions, but the fraction containing larger-sized chains had higher antithrombin III-binding affinity. (c) 2018 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.

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