Synthetic heparin and heparan sulfate: probes in defining biological functions

•Heparin and heparan sulfate binds various proteins and modulate their activity.•Advances allowed the chemical preparation of long sugars and sugar libraries.•Anticoagulant heparin oligomers have been achieved by chemoenzymatic synthesis.•Computational methods and MS analysis pinpoint specific seque...

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Bibliographic Details
Published in:Current opinion in chemical biology 2017-10, Vol.40, p.152-159
Main Authors: Tsai, Ching-Ting, Zulueta, Medel Manuel L, Hung, Shang-Cheng
Format: Article
Language:English
Subjects:
Animals
Anticoagulants - chemical synthesis
Anticoagulants - chemistry
Anticoagulants - metabolism
Anticoagulants - pharmacology
Blood Coagulation - drug effects
Chemistry Techniques, Synthetic - methods
Drug Discovery
Heparin - chemical synthesis
Heparin - chemistry
Heparin - metabolism
Heparin - pharmacology
Heparitin Sulfate - chemical synthesis
Heparitin Sulfate - chemistry
Heparitin Sulfate - metabolism
Heparitin Sulfate - pharmacology
Humans
Models, Molecular
Proteins - metabolism
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Summary:•Heparin and heparan sulfate binds various proteins and modulate their activity.•Advances allowed the chemical preparation of long sugars and sugar libraries.•Anticoagulant heparin oligomers have been achieved by chemoenzymatic synthesis.•Computational methods and MS analysis pinpoint specific sequences for synthesis. Heparin and heparan sulfate are glycosaminoglycans that modulate numerous biological processes. The desire to capture the structural diversity responsible for their functions provides notable issues during synthesis, including site-selective sulfonation, stereoselective glycosylation and the sheer number of probable targets at hand. With current advances in synthetic approaches, carbohydrate chemists generate these complex targets by chemical and enzymatic methods. Fondaparinux and a number of polysaccharides have been synthesized to probe anticoagulation and other biological functions. Moreover, a trove of structural information could be obtained by many analytical methods, which provide hints to the potential protein-binding sequences within the sugar chain. Further structure–activity relationship studies help unveil the secrets of the heparin/heparan sulfate code, providing potential candidates for drug development.
ISSN:1367-5931
1879-0402
DOI:10.1016/j.cbpa.2017.09.012