Stereoselective Chemoenzymatic Synthesis of UDP‐1,2‐<i>cis</i>‐furanoses from α,β‐Furanosyl 1‐Phosphates

Peltier, Pauline; Guégan, Jean‐Paul; Daniellou, Richard; Nugier‐Chauvin, Caroline; Ferrières, Vincent

doi:10.1002/ejoc.200800742

Cited by 16 publications

(13 citation statements)

References 25 publications

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“…In this process, α‐Gal f 1‐phosphate (Scheme , 11 )61 is converted into UDP‐Gal f by the enzyme galactose‐1‐phosphate uridinyltransferase (GalPUT); 30 mg of UDP‐Gal f can be obtained from 11 after HPLC purification. Recently, Peltier et al probed the specificity of GalPUT 62. The enzyme accepts a variety of furanoside phosphates, including D ‐galactose, 6‐deoxy‐6‐fluoro‐ D ‐galactose, D ‐fucose and L ‐arabinose, but neither D ‐glucofuranose nor D ‐mannofuranose serve as substrates.…”

Section: Biosynthesis Of Galf Residuesmentioning

confidence: 99%

Chemistry and Biology of Galactofuranose‐Containing Polysaccharides

2009

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The thermodynamically less stable form of galactose-galactofuranose (Galf)-is essential for the viability of several pathogenic species of bacteria and protozoa but absent in this form in mammals, so the biochemical pathways by which Galf-containing glycans are assembled and catabolysed are attractive sites for drug action. This potential has led to increasing interest in the synthesis of molecules containing Galf residues, their subsequent use in studies directed towards understanding the enzymes that process these residues and the identification of potential inhibitors of these pathways. Major achievements of the past several years have included an in-depth understanding of the mechanism of UDP-galactopyranose mutase (UGM), the enzyme that produces UDP-Galf, which is the donor species for galactofuranosyltransferases. A number of methods for the synthesis of galactofuranosides have also been developed, and practitioners in the field now have many options for the initiation of a synthesis of glycoconjugates containing either alpha- or beta-Galf residues. UDP-Galf has also been prepared by a number of approaches, and it appears that a chemoenzymatic approach is currently the most viable method for producing multi-milligram amounts of this important intermediate. Recent advances both in the understanding of the mechanism of UGM and in the synthesis of galactofuranose and its derivatives are highlighted in this review.

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Section: Biosynthesis Of Galf Residuesmentioning

confidence: 99%

Chemistry and Biology of Galactofuranose‐Containing Polysaccharides

2009

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“…The importance for in vivo galactofuranosylation is shown by a targeted gene deletion approach. (24).…”

Section: In Vitro Transport Assays Established Binding Of Udp-galf Tomentioning

confidence: 99%

“…Large particles (whole cells, nuclei, and mitochondria) were removed by two sequential centrifugation steps (30 min at 10,000 ϫ g and 20 min at 27,000 ϫ g) and microsomes were pelleted at 110,000 ϫ g (45 min) at 4°C. The microsomal pellet was suspended in 800 l of lysis buffer, applied on a multistep sucrose gradient (1 ml of each 60,50,40,38,36,34,32,30,28,26,24,20,18, and 15% (w/w) sucrose in 10 mM HEPES/Tris, pH 7.4, and 1 mM EDTA) and centrifuged at 110,000 ϫ g for 16 h at 4°C. Fractions (approximately 0.5 ml) were collected from the bottom of the tube and kept at 4°C until analyzed.…”

Section: Materials-radiolabeledmentioning

confidence: 99%

A Single UDP-galactofuranose Transporter Is Required for Galactofuranosylation in Aspergillus fumigatus

Engel

Schmalhorst

Dörk

et al. 2009

Journal of Biological Chemistry

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Galactofuranose (Galf) containing molecules have been described at the cell surface of several eukaryotes and shown to contribute to the virulence of the parasite Leishmania major and the fungus Aspergillus fumigatus. It is anticipated that a number of the surface glycoconjugates such as N-glycans or glycolipids are galactofuranosylated in the Golgi apparatus. This raises the question of how the substrate for galactofuranosylation reactions, UDP-Galf, which is synthesized in the cytosol, translocates into the organelles of the secretory pathway. Here we report the first identification of a Golgi-localized nucleotide sugar transporter, named GlfB, with specificity for a UDP-Galf. In vitro transport assays established binding of UDP-Galf toGlfB and excluded transport of several other nucleotide sugars. Furthermore, the implication of glfB in the galactofuranosylation of A. fumigatus glycoconjugates and galactomannan was demonstrated by a targeted gene deletion approach. Our data reveal a direct connection between galactomannan and the organelles of the secretory pathway that strongly suggests that the cell wall-bound polysaccharide originates from its glycosylphosphatidylinositol-anchored form.

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“…Therefore, structurally well-defined synthetic analogues are of great interest for the development of new pharmacophores and new therapies. [6][7][8][9] Some of them have been proven to present antigenic properties. For instance, b-D-Galf O-linked oligosaccharides, found in Penicillium and Aspergillus species, appeared to be immunodominant.…”

Section: Introductionmentioning

confidence: 99%

Enzymatic synthesis of oligo-d-galactofuranosides and l-arabinofuranosides: from molecular dynamics to immunological assays

et al. 2010

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D-Galactofuranosyl-containing conjugates are ubiquitous in many pathogenic microorganisms, but completely absent from mammals. As they may constitute interesting pharmacophores, recent works have been dedicated to their preparation. Besides well-reported chemical procedures, enzymatic approaches are still limited, mainly due to the lack of the corresponding biocatalysts. Based on the similarity between chemical structures, the arabinofuranosyl hydrolase Araf51 from Clostridium thermocellum was expected to recognize both the L-Araf motif and its D-Galf analogue. Molecular dynamics and STD-NMR were firstly used to confirm this hypothesis and increase our knowledge of the active site. Interestingly, this arabinofuranosidase was not only able to hydrolyze galactosyl derivatives, but was also really efficient in catalyzing oligomerisations using p-nitrophenyl furanosides as donors. The structures of the products obtained were determined using mass spectrometry and NMR. Amongst them, all the possible regioisomers of di-arabino and -galactofuranosides were synthesized, and the ratio of each regioisomer was easily tuned with respect to the reaction time. Especially, the galactofuranobioside displaying the biologically relevant sequence beta-D-Galf-(1,6)-beta-D-Galf was enzymatically prepared for the first time. All fractions going from di- to penta-arabino- and galactofuranosides were tested for their ability in eliciting the production of TNF-alpha. Interesting immunological properties were observed with arabinofuranosides as short as three sugar residues.

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Stereoselective Chemoenzymatic Synthesis of UDP‐1,2‐cis‐furanoses from α,β‐Furanosyl 1‐Phosphates

Cited by 16 publications

References 25 publications

Chemistry and Biology of Galactofuranose‐Containing Polysaccharides

Chemistry and Biology of Galactofuranose‐Containing Polysaccharides

A Single UDP-galactofuranose Transporter Is Required for Galactofuranosylation in Aspergillus fumigatus

Enzymatic synthesis of oligo-d-galactofuranosides and l-arabinofuranosides: from molecular dynamics to immunological assays

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