Chemoenzymatic synthesis of homogeneous ultralow molecular weight heparins

Yongmei Xu, Sayaka Masuko, Majde Takieddin, Haoming Xu, Renpeng Liu, Juliana Jing, Shaker A. Mousa, Robert J. Linhardt, Jian Liu

Research output: Contribution to journalArticlepeer-review

348 Scopus citations

Abstract

Ultralow molecular weight (ULMW) heparins are sulfated glycans that are clinically used to treat thrombotic disorders. ULMW heparins range from 1500 to 3000 daltons, corresponding from 5 to 10 saccharide units. The commercial drug Arixtra (fondaparinux sodium) is a structurally homogeneous ULMW heparin pentasaccharide that is synthesized through a lengthy chemical process. Here, we report 10- and 12-step chemoenzymatic syntheses of two structurally homogeneous ULMW heparins (MW = 1778.5 and 1816.5) in 45 and 37% overall yield, respectively, starting from a simple disaccharide. These ULMW heparins display excellent in vitro anticoagulant activity and comparable pharmacokinetic properties to Arixtra, as demonstrated in a rabbit model. The chemoenzymatic approach is scalable and shows promise for a more efficient route to synthesize this important class of medicinal agent.

Original languageEnglish
Pages (from-to)498-501
Number of pages4
JournalScience
Volume334
Issue number6055
DOIs
StatePublished - 28 Oct 2011
Externally publishedYes

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