Large-scale chemoenzymatic synthesis of blood group and tumor-associated poly-N-acetyllactosamine antigens

Vasiliu, Daniela; Razi, Nahid; Zhang, Yingning; Jacobsen, Nathan; Allin, Kirk; Liu, Xiaofei; Hoffmann, Julia; Bohorov, Ognian; Blixt, Ola

doi:10.1016/j.carres.2006.03.043

Cited by 43 publications

(32 citation statements)

References 30 publications

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“…With enzymatic methods higher yields and absolute selectivity are achieved along with recycling protocols for biocatalysts and donor substrates during the synthesis of complex saccharide structures [25][26][27]. This was impressively demonstrated by Blixt et al with a large-scale enzymatic synthesis of polyLacNAc based glycan structures using bacterial enzyme systems including LgtA (β1-4galactosyltransferase, β4GalT) and LgtB from Neisseria meningitidis (β1-3N-acetyl-glucosaminyltransferase, β3GlcNAcT) [17,28,29]. Other groups utilized enzymes from bovine milk (β4GalT) and human serum (β3GlcNAcT) [8,9,30].…”

Section: Introductionmentioning

confidence: 93%

“…Both sugar derivatives provide a linker at their reducing end for immobilization onto surfaces. The use of the azidogroup for the immobilization to surfaces is well described [17]. However, GlcNAc-linker-NH 2 -tBoc 7 has some advantages as acceptor for the enzymatic synthesis.…”

Section: Chemical Synthesis Of Functionalized β-N-acetylglucosaminidesmentioning

confidence: 99%

“…We describe here a suitable strategy for the chemoenzymatic synthesis of defined poly-LacNAc structures and their immobilization onto surfaces with an appropriate orthogonal linker. The chemo-enzymatic synthesis of polyLacNAc structures has been reported using modified and natural acceptor substrates in combination with recombinant and commercial glycosyltransferases as well as endo-β-galactosidases [8,[16][17][18][19]. In order to make functionalized carbohydrate derivatives we employed chemical synthesis for the linker which is still time-consuming with several protection and deprotection steps [20].…”

Section: Introductionmentioning

confidence: 99%

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Chemo-enzymatic synthesis of poly-N-acetyllactosamine (poly-LacNAc) structures and their characterization for CGL2-galectin-mediated binding of ECM glycoproteins to biomaterial surfaces

et al. 2008

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Poly-N-acetyllactosamine (poly-LacNAc) structures have been identified as important ligands for galectin-mediated cell adhesion to extra-cellular matrix (ECM) proteins. We here present the biofunctionalization of surfaces with poly-LacNAc structures and subsequent binding of ECM glycoproteins. First, we synthesized beta-GlcNAc glycosides carrying a linker for controlled coupling onto chemically functionalized surfaces. Then we produced poly-LacNAc structures with defined lengths using human beta1,4-galactosyltransferase-1 and beta1,3-N-acetylglucosaminyltransferase from Helicobacter pylori. These compounds were also used for kinetic characterization of glycosyltransferases and lectin binding assays. A mixture of poly-LacNAc-structures covalently coupled to functionalized microtiter plates were identified for best binding to our model galectin His(6)CGL2. We further demonstrate for the first time that these poly-LacNAc surfaces are suitable for further galectin-mediated binding of the ECM glycoproteins laminin and fibronectin. This new technology should facilitate cell adhesion to biofunctionalized surfaces by imitating the natural ECM microenvironment.

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Section: Introductionmentioning

confidence: 93%

Section: Chemical Synthesis Of Functionalized β-N-acetylglucosaminidesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Chemo-enzymatic synthesis of poly-N-acetyllactosamine (poly-LacNAc) structures and their characterization for CGL2-galectin-mediated binding of ECM glycoproteins to biomaterial surfaces

et al. 2008

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“…Poor selectivity of fucoside coupling reactions and tedious protecting group manipulations are major challenges for synthetic chemists preparing these formidable targets. In contrast, enzymatic glycosylation by fucosyltransferases overcomes laborious and expensive chemical routes and produces Lewis antigen-containing glycans in a regio-and stereospecific manner (13). This approach requires fucose or its synthetic analogs in the nucleotide-activated form-guanidine 5Ј-diphosphate-␤-L-fucose (GDP-fucose) analogs-as the substrate for fucosyltransferases.…”

mentioning

confidence: 99%

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

Wang¹,

Hu²,

Frantom³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

123

100

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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-␤-L-fucose (GDPfucose), 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 ␣1,3 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.glycobiology ͉ catalysis ͉ enzyme

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“…44 Recently, the synthesis of a variety of biologically relevant sialyl oligosaccharides was facilitated by a number of chemoenzymatic strategies using bacterial glycosyltransferases. [45][46][47][48][49][50][51] Thus, several glycosyltransferase genes from C. jejuni have been expressed in E. coli and methods for the efficient synthesis of 2-azidoethyl glycosides corresponding to the oligosaccharides of GD3, GT3, GM2, GD2, GT2, GM1 and GD1a were developed with a water-soluble 2-azidoethyl lactoside as starting compound. 52,53 For the application of such materials into sensing devices, attachment of other than highly water-soluble chains would, however, be a big step forward.…”

Section: Introductionmentioning

confidence: 99%

GM3, GM2 and GM1 mimics designed for biosensing: chemoenzymatic synthesis, target affinities and 900MHz NMR analysis

Pukin

Weijers

Lagen

et al. 2008

Carbohydrate Research

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Abstract-Undec-10-enyl, undec-10-ynyl and 11-azidoundecyl glycoside analogues corresponding to the oligosaccharides of human gangliosides GM3, GM2 and GM1 were synthesized in high yields using glycosyltransferases from Campylobacter jejuni. Due to poor water solubility of the substrates, the reactions were carried out in methanol-water media, which for the first time were shown to be compatible with the C. jejuni a-(2?3)-sialyltransferase (CST-06) and b-(1?4)-N-acetylgalactosaminyltransferase (CJL-30). Bioequivalence of our synthetic analogues and natural gangliosides was examined by binding to Vibrio cholerae toxin and to the B subunit of Escherichia coli heat-labile enterotoxin. This bioequivalence was confirmed by binding mouse and human monoclonal antibodies to GM1 and acute phase sera containing IgM and IgG antibodies to GM1 from patients with the immune-mediated polyneuropathy Guillain-Barré syndrome. The synthesized compounds were analyzed by 1D and 2D 900 MHz NMR spectroscopy. TOCSY and DQF-COSY experiments in combination with 13 C-1 H correlation measurements (HSQC, HMBC) were carried out for primary structural characterization, and a complete assignment of all 1 H and 13 C chemical shifts is presented.

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Large-scale chemoenzymatic synthesis of blood group and tumor-associated poly-N-acetyllactosamine antigens

Cited by 43 publications

References 30 publications

Chemo-enzymatic synthesis of poly-N-acetyllactosamine (poly-LacNAc) structures and their characterization for CGL2-galectin-mediated binding of ECM glycoproteins to biomaterial surfaces

Chemo-enzymatic synthesis of poly-N-acetyllactosamine (poly-LacNAc) structures and their characterization for CGL2-galectin-mediated binding of ECM glycoproteins to biomaterial surfaces

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

GM3, GM2 and GM1 mimics designed for biosensing: chemoenzymatic synthesis, target affinities and 900MHz NMR analysis

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