Investigation of the biological functions of heparan sulfate using a chemoenzymatic synthetic approach

利用化学酶法合成方法研究硫酸乙酰肝素的生物学功能

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Abstract

Heparan sulfate (HS) is a highly sulfated polysaccharide playing essential physiological and pathophysiological roles in the animal kingdom. Heparin, a highly sulfated form of HS, is a widely used anticoagulant drug. Isolated from biological sources, both heparin and HS are polysaccharide mixtures with different sugar chain lengths and sulfation patterns. Structural heterogeneity of HS complicates the investigation of HS-related biological activities. The availability of structurally defined HS oligosaccharides is critical in understanding the contribution of saccharide structures to the functions. The chemoenzymatic synthetic approach is emerging as a cost-effective method to synthesize HS oligosaccharides. Structurally defined oligosaccharides are now widely available for biologists. This review summarizes our efforts in using this new synthetic method to develop new anticoagulant therapeutics and discover the role of HS to protect liver damage under pathological conditions. The synthetic method also allows us to prepare reference saccharide standards to improve structural analysis of HS.

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