Heparin is a linear, highly anionic polysaccharide, displaying a number of prominent biological activities such as growth factor, chemokine signaling and anticoagulant activity. Due to the safety concern of animal-sourced heparin, preparation of a more structurally defined heparin oligosaccharide is highly desirable. Our research was divided into two parts here. In the first part, we successfully prepared an unmodified heparin pentasaccharide through a chemoenzymatic synthesis using p-nitrophenyl glucuronide (GlcA-pNP) as a glycosylation acceptor, followed by Smith degradation or alkaline elimination to selectively remove GlcA-pNP moiety from the reducing end of the molecule. This is the first time these two degradation methods has been applied to the preparative synthesis of an oligosaccharide. In the second part, in order to synthesize heparan sulfate/heparin oligosaccharides of defined sequence length, we successfully completed the synthesis of UDP-4FGlcNAc/-4FGalNAc analogs using both an improved chemical method as well as a new chemoenzymatic approach. To our delight, UDP-4FGlcNAc could be transferred onto an acceptor by Pastuerella Multocida heparan sulfate synthese-1 and subsequently served as a chain terminator.

Chemoenzymatic synthesis of novel heparan sulfate and heparin oligosaccharides

254th National Meeting (2017)

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