ABSTRACT
Heparan sulfate (HS) takes part in regulation of many related animal biological functions by its interaction with proteins and plays an important role. As a special structure type of HS, heparin (HP) is also widely used as clinical anticoagulant drug and demonstrated to be a promising candidate for anticancer and anti-inflammatory drugs. Natural HS and HP are highly heterogeneous mixtures differing in their polysaccharide chain lengths, sulfation patterns and so on, which restricts elucidation of the relationship between their structures and functions and further application of their drug potential. There has recently been a breakthrough in chemoenzymatic method developed for an alternative approach different from chemical synthesis, which shortens the synthesis and improves the product yields significantly. Application of chemoenzymatic synthesis accelerates elucidation of structure-function relationships in HS/HP and low-molecular-weight heparins (LMWH) with reversible anticoagulative activity have been obtained. Along with improvement and optimization of chemoenzymatic method and further understanding of structure-function relationship, it will gradually become possible to synthesize structure-specific HS/HP drugs with better and more stable effects and less adverse effects in the future. Recent progress of HS/HP chemoenzymatic synthesis is summarized in this review.
ABSTRACT
Heparan sulfate (HS)takes part in regulation of many related animal biological functions by its interaction with proteins and plays an important role. As a special structure type of HS,heparin (HP)is also widely used as clinical anticoagulant drug and demonstrated to be a promising candidate for anticancer and anti-inflammatory drugs. Natural HS and HP are highly heterogeneous mixtures differing in their polysaccharide chain lengths,sulfation patterns and so on,which restricts elucidation of the relationship between their structures and functions and further application of their drug potential. There has recently been a breakthrough in chemoenzymatic method developed for an alternative approach different from chemical synthesis,which shortens the synthesis and improves the product yields significantly. Application of chemoenzymatic synthesis accelerates elucidation of structure-function relationships in HS/HP and low-molecular-weight heparins (LMWH) with reversible anticoagulative activity have been obtained. Along with improvement and optimization of chemoenzymatic method and further understanding of structure-function relationship,it will gradually become possible to synthesize structure-specific HS/HP drugs with better and more stable effects and less adverse effects in the future. Recent progress of HS/HP chemoenzymatic synthesis is summarized in this review.