End-Site-Specific Conjugation of Enoxaparin and Tetradeoxycholic Acid Using Nonenzymatic Glycosylation for Oral Delivery

Jooho Park, Ok Cheol Jeon, Jisuk Yun, Hwajung Nam, Jinha Hwang, Taslim A. Al-Hilal, Kwang Meyung Kim, Kyungjin Kim, Youngro Byun

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Heparin and low molecular weight heparins (LMWHs) have been the drug of choice for the treatment or the prevention of thromboembolic disease. Different methods are employed to prepare the LMWHs that are clinically approved for the market currently. In particular, enoxaparin, which has a reducing sugar moiety at the end-site of polysaccharide, is prepared by alkaline depolymerization. Focusing on this end-site-specific activity of LMWHs, we conjugated the tetraoligomer of deoxycholic acid (TetraDOCA; TD) at the end-site of enoxaparin via nonenzymatic glycosylation reaction. The end-site-specific conjugation is important for polysaccharide drug development because of the heterogeneity of polysaccharides. This study also showed that orally active enoxaparin and tetraDOCA conjugate (EnoxaTD) had therapeutic effect on deep vein thrombosis (DVT) without bleeding in animal models. Considering the importance of end-specific conjugation, these results suggest that EnoxaTD could be a drug candidate for oral heparin development.

Original languageEnglish
Pages (from-to)10520-10529
Number of pages10
JournalJournal of Medicinal Chemistry
Issue number23
Publication statusPublished - 2016 Dec 8
Externally publishedYes


ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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