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

Xing Zhang, Yongmei Xu, Po Hung Hsieh, Jian Liu, Lei Lin, Eric P. Schmidt, Robert J. Linhardt

Research output: Contribution to journalArticle

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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 glucuronic acid residues affording highly sulfated heparin pentasaccharides 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.

LanguageEnglish (US)
Pages1222-1227
Number of pages6
JournalOrganic and Biomolecular Chemistry
Volume15
Issue number5
DOIs
StatePublished - Jan 1 2017

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heparins
Glucuronides
Oligosaccharides
Heparin
cleavage
degradation
Degradation
synthesis
acids
purification
Glucuronic Acid
resins
elimination
recovery
methodology
Purification
oxidation
Resins
evaluation
Recovery

ASJC Scopus subject areas

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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Chemoenzymatic synthesis of unmodified heparin oligosaccharides : cleavage of p-nitrophenyl glucuronide by alkaline and Smith degradation. / Zhang, Xing; Xu, Yongmei; Hsieh, Po Hung; Liu, Jian; Lin, Lei; Schmidt, Eric P.; Linhardt, Robert J.

In: Organic and Biomolecular Chemistry, Vol. 15, No. 5, 01.01.2017, p. 1222-1227.

Research output: Contribution to journalArticle

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