Controlled Chemoenzymatic Synthesis of Heparan Sulfate Oligosaccharides

A chemoenzymatic approach has been developed for the preparation of diverse libraries of heparan sulfate (HS) oligosaccharides. It employs chemically synthesized oligosaccharides having a chemical entity at a GlcN residue, which in unanticipated manners influences the site of modification by NST, C5...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2018-05, Vol.57 (19), p.5340-5344
Main Authors: Lu, Weigang, Zong, Chengli, Chopra, Pradeep, Pepi, Lauren E., Xu, Yongmei, Amster, I. Jonathan, Liu, Jian, Boons, Geert‐Jan
Format: Article
Language:English
Subjects:
Carbohydrate Conformation
Chemical synthesis
enzymes
epimers
heparan
Heparan sulfate
Heparitin Sulfate - biosynthesis
Heparitin Sulfate - chemistry
Oligosaccharides
Oligosaccharides - biosynthesis
Oligosaccharides - chemistry
Substrates
Sulfates
Sulfation
Sulfotransferases - chemistry
Sulfotransferases - metabolism
synthetic methods
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Summary:A chemoenzymatic approach has been developed for the preparation of diverse libraries of heparan sulfate (HS) oligosaccharides. It employs chemically synthesized oligosaccharides having a chemical entity at a GlcN residue, which in unanticipated manners influences the site of modification by NST, C5‐Epi/2‐OST and 6‐OST1/6‐OST3, thus resulting in oligosaccharides differing in N/O‐sulfation and epimerization pattern. The enzymatic transformations defined fine substrate requirements of NST, C5‐Epi, 2‐OST, and 6‐OST. Sugar patterns: Enzymatic modifications of three chemically synthesized hexasaccharides, with or without a 6‐O‐methyl ether on a GlcN residue, using NST, C5‐Epi/2‐OST, and 6‐OST1/6‐OST3 gave, in an expeditious way, a library of 21 hexasaccharides that differ in N/O‐sulfation and epimerization pattern. The enzymatic transformations defined fine substrate requirements of NST, C5‐Epi, 2‐OST, and 6‐OST. Epi=epimerase, NST=N‐sulfotransferase, OST=O‐sulfotransferase.
ISSN:1433-7851
1521-3773
1521-3773
DOI:10.1002/anie.201800387