The versatile enzyme Araf51 allowed efficient synthesis of rare pathogen-related β-d-galactofuranosyl-pyranoside disaccharides

Abstract

The preparation of galactofuranosyl-containing disaccharidic parts of natural glycoconjugates was performed according to a chemo-enzymatic synthesis. Our goals were firstly to develop an alternative approach to standard chemical strategies by limiting the number of reaction and purification steps, and secondly to evaluate the scope of the Araf51 biocatalyst to transfer a galactofuranosyl moiety to a set of pyranosidic acceptors differing from each other by the series, the anomeric configuration as well as the conformation. The study of binding mode of the resulting disaccharides was also performed by molecular modeling and showed significant differences between (1→2)- and (1→6)-linked disaccharides.

Regioselective Galactofuranosylation for the Synthesis of Disaccharide Patterns Found in Pathogenic Microorganisms

“…8−13 Alternatively galactofuranosyl-transferases isolated from mycobacteria or furanosylhydrolases involved in the degradation of biomass have been used to obtain either oligomers of Galf 14,15 or heterodisaccharides. 16,17 These last strategies involve a minimum of protecting group manipulation as biocatalysts are able to selectively transfer a furanosyl entity on a specific position of an acceptor.…”

“…Intriguingly some microorganisms incorporate carbohydrates in their furanose form rather than in their pyranose one in order to further differentiate themselves from other organisms. , In particular d -galactofuranose ( d -Gal f ) containing glycoconjugates are found in large amount in pathogenic microorganisms like Mycobacteria or Leishmania but are absent in the mammalian kingdom . Owing to the key role played by such motifs in the virulence or survival of the parasite or bacteria, numerous groups have developed evolved synthetic pathways to access to such Gal f -containing oligosaccharides. − Alternatively galactofuranosyl-transferases isolated from mycobacteria or furanosylhydrolases involved in the degradation of biomass have been used to obtain either oligomers of Gal f , or heterodisaccharides. , These last strategies involve a minimum of protecting group manipulation as biocatalysts are able to selectively transfer a furanosyl entity on a specific position of an acceptor.…”

Diversion of a thioglycoligase for the synthesis of 1-O-acyl arabinofuranoses

“…26 Latter on Ferrières and co-workers used this enzyme as efficient biocatalyst in both self-condensation and transglycosylation of L-arabinofuranose donor. 27,28 Furthermore, CtAraf51 was successfully transformed into the corresponding thioligase by the mutation of the glutamic acid 173 into the alanine. The resulting mutant CtAraf51 E173A was able to recognize a thioimidoyl arabinofuranoside 1 as a donor and transfer the furanose to different thiophenol via a remote activation mechanism.…”