Chemoenzymatic synthesis of unmodified heparin oligosaccharides: Cleavage of p-nitrophenyl glucuronide by alkaline and Smith degradation

Loading...
Thumbnail Image
Authors
Zhang, Xing
Xu, Yongmei
Hsieh, Po Hung
Liu, Jian
Lin, Lei
Schmidt, Eric P.
Linhardt, Robert J.
Issue Date
2017-01-01
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Research Projects
Organizational Units
Journal Issue
Alternative Title
Abstract
A heparin oligosaccharide having a completely natural structure was successfully synthesized through a chemoenzymatic approach using an unnatural glycosyl acceptor, p-nitrophenyl glucuronide (GlcA-pNP). The use of an inexpensive and commercially available GlcA-pNP acceptor facilitates oligosaccharide recovery and purification on C-18 resin during chemoenzymatic synthesis. Oligosaccharide chain extension and modification afforded a heptasaccharide with gluconic acid residues at its reducing and non-reducing ends. Treatment with periodate oxidation followed by Smith degradation or alkaline elimination resulted in the selective cleavage of vicinal diol-containing glucronic acid residues affording highly sulfated heparin pentasaccharide having a completely natural structure. This methodology should facilitate the chemoenzymatic synthesis of a family of highly sulfated heparin oligosaccharides with unmodified structures for biological evaluation.
Description
Organic and Biomolecular Chemistry, 15, 1222–1227
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Full Citation
Chemoenzymatic synthesis of unmodified heparin oligosaccharides: Cleavage of p-nitrophenyl glucuronide by alkaline and Smith degradation, X. Zhang, Y. Xu, J. Liu, L. Lin, E. Schmidt, R.J. Linhardt, Organic and Biomolecular Chemistry, 15, 1222–1227, 2017.
Publisher
Royal Society of Chemistry
Terms of Use
Journal
Volume
Issue
PubMed ID
DOI
ISSN
14770520
EISSN