Chemoenzymatic synthesis of GDP-L-fucose and the Lewis X glycan derivatives

Wei Wang, Tianshun Hu, Patrick A. Frantom, Tianqing Zheng, Brian Gerwe, David Soriano Del Amo, Sarah Garret, Ronald D. Seidel, Peng Wu

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Lewis X (Lex)-containing glycans play important roles in numerous cellular processes. However, the absence of robust, facile, and cost-effective methods for the synthesis of Lex and its structurally related analogs has severely hampered the elucidation of the specific functions of these glycan epitopes. Here we demonstrate that chemically defined guanidine 5′-diphosphate-β-L-fucose (GDP-fucose), the universal fucosyl donor, the Lex trisaccharide, and their C-5 substituted derivatives can be synthesized on preparative scales, using a chemoenzymatic approach. This method exploits L-fucokinase/GDP-fucose pyrophosphorylase (FKP), a bifunctional enzyme isolated from Bacteroides fragilis 9343, which converts L-fucose into GDP-fucose via a fucose-1-phosphate (Fuc-1-P) intermediate. Combining the activities of FKP and a Helicobacter pylori α1,3 fucosyltransferase, we prepared a library of Lex trisaccharide glycans bearing a wide variety of functional groups at the fucose C-5 position. These neoglycoconjugates will be invaluable tools for studying Lex-mediated biological processes.

Original languageEnglish (US)
Pages (from-to)16096-16101
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number38
DOIs
StatePublished - Sep 22 2009

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Guanosine Diphosphate Fucose
Fucose
fucokinase
Polysaccharides
Diphosphates
Guanidine
galactoside 3-fucosyltransferase
Biological Phenomena
Bacteroides fragilis
Helicobacter pylori
Libraries
Epitopes
Costs and Cost Analysis
Enzymes

Keywords

  • Catalysis
  • Enzyme
  • Glycobiology

ASJC Scopus subject areas

  • General

Cite this

Chemoenzymatic synthesis of GDP-L-fucose and the Lewis X glycan derivatives. / Wang, Wei; Hu, Tianshun; Frantom, Patrick A.; Zheng, Tianqing; Gerwe, Brian; Del Amo, David Soriano; Garret, Sarah; Seidel, Ronald D.; Wu, Peng.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 38, 22.09.2009, p. 16096-16101.

Research output: Contribution to journalArticle

Wang, W, Hu, T, Frantom, PA, Zheng, T, Gerwe, B, Del Amo, DS, Garret, S, Seidel, RD & Wu, P 2009, 'Chemoenzymatic synthesis of GDP-L-fucose and the Lewis X glycan derivatives', Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 38, pp. 16096-16101. https://doi.org/10.1073/pnas.0908248106
Wang, Wei ; Hu, Tianshun ; Frantom, Patrick A. ; Zheng, Tianqing ; Gerwe, Brian ; Del Amo, David Soriano ; Garret, Sarah ; Seidel, Ronald D. ; Wu, Peng. / Chemoenzymatic synthesis of GDP-L-fucose and the Lewis X glycan derivatives. In: Proceedings of the National Academy of Sciences of the United States of America. 2009 ; Vol. 106, No. 38. pp. 16096-16101.
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