Enzymatic synthesis of oligo-D-galactofuranosides and l-arabinofuranosides: from molecular dynamics to immunological assays. - Université de Rennes Accéder directement au contenu
Article Dans Une Revue Organic & Biomolecular Chemistry Année : 2010

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

Résumé

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.

Domaines

Chimie organique

Dates et versions

hal-00757165 , version 1 (26-11-2012)

Identifiants

Citer

Ilona Chlubnová, Dominik Filipp, Vojtech Spiwok, Hana Dvoráková, Richard Daniellou, et al.. Enzymatic synthesis of oligo-D-galactofuranosides and l-arabinofuranosides: from molecular dynamics to immunological assays.. Organic & Biomolecular Chemistry, 2010, 8 (9), pp.2092-102. ⟨10.1039/b926988f⟩. ⟨hal-00757165⟩
38 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More