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

Full Abstract

Lewis X (Le(x))-containing glycans play important roles in numerous cellular processes. However, the absence of robust, facile, and cost-effective methods for the synthesis of Le(x) 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-beta-l-fucose (GDP-fucose), the universal fucosyl donor, the Le(x) 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 alpha1,3 fucosyltransferase, we prepared a library of Le(x) trisaccharide glycans bearing a wide variety of functional groups at the fucose C-5 position. These neoglycoconjugates will be invaluable tools for studying Le(x)-mediated biological processes.

Author information

Author/s: Wang, Wei (W); Hu, Tianshun (T); Frantom, Patrick A (PA); Zheng, Tianqing (T); Gerwe, Brian (B); Del Amo, David Soriano (DS); Garret, Sarah (S); Seidel, Ronald D (RD); Wu, Peng (P);

Affiliation: Department of Biochemistry and Macromolecular Therapeutics Development Facility, Albert Einstein College of Medicine, Yeshiva University, 1300 Morris Park Avenue, Bronx, NY 10461, USA.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A), published in United States. (Language: eng)

Reference: 2009-Sep; vol 106 (issue 38) : pp 16096-101

Dates: Created 2009/10/06; Completed 2009/11/06;

PMID: 19805264, status: MEDLINE (last retrieval date: 11/6/2009, IMS Date: )

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Associated Chemicals: Antigens, CD15 (0) ; Bacterial Proteins (0) ; Polysaccharides (0) ; Guanosine Diphosphate Fucose (15839-70-0) ; Adenosine Triphosphate (56-65-5) ; Guanosine Triphosphate (86-01-1) ; Phosphotransferases (Alcohol Group Acceptor) (EC 2.7.1.-) ; fucokinase (EC 2.7.1.52) ; GDP-L-fucose pyrophosphorylase (EC 2.7.7.-) ; Nucleotidyltransferases (EC 2.7.7.-)

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