Facile chemoenzymatic synthesis of unmodified anticoagulant ultra-low molecular weight heparin. Issue 42 (14th October 2022)

• Record Type: Journal Article
• Authors: Zhang, Guijiao; Yang, Kaihua; Wang, Lin; Cheng, Yanzhen; Liu, Chunhui
• Is Part Of: Organic & biomolecular chemistry. Volume 20:Issue 42(2022)
• Page Start: 8323
• Page End: 8330
• Publication Date: 2022-10-14
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/d2ob01221a
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : A chemoenzymatic approach, mimicking the biosynthetic pathway of heparin and heparan sulfate (HS), has been well developed to prepare a series of structurally well-defined heparin oligosaccharides with excellent anticoagulant activity in good overall yields. Abstract : A chemoenzymatic approach, mimicking the biosynthetic pathway of heparin and heparan sulfate (HS), has been well developed to prepare a series of structurally well-defined heparin oligosaccharides with excellent anticoagulant activity in good overall yields. The current chemoenzymatic synthesis typically begins with an unnatural glycosyl acceptor, p -nitrophenyl glucuronide (GlcA-PNP), which is convenient for detection recovery and purification, although it affords heparin molecules with undesirable structure characteristics. Herein, we describe a facile chemoenzymatic strategy assisted by the specific cleavage of heparinase III for the highly efficient synthesis of an unmodified heparin heptasaccharide which demonstrated potent anticoagulant activity in vitro and commensurate pharmacokinetic profiles with fondaparinux. This successful generic strategy is applicable to the scalable synthesis of diverse HS/heparin molecules with completely natural structural features as promising therapeutic agents.