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, Kwangmeyung Kim, Kyungjin Kim, Youngro Byun

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


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

Bibliographical note

Funding Information:
This work was supported by Korea Drug Development Fund (Grant KDDF-201408-03). This study was also supported by Basic Science Research Program (Grant 2010-0027955) of the National Research Foundation of Korea (NRF) and Cancer Control (Grant 1420390), Ministry of Health and Welfare.

Publisher Copyright:
© 2016 American Chemical Society.

Copyright 2017 Elsevier B.V., All rights reserved.

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery


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