Synthesis of new sulfated disaccharides for the modulation of TLR4-dependent inflammation.

Rachid Naïtaleb, Agnès Denys, Fabrice Allain, Jérôme Ausseil, Sylvestre Toumieux, José Kovensky

Organic & biomolecular chemistry 2021 May 21

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Natural sulfated glycans are key players in inflammation through TLR4 activation; therefore synthetic exogenous sulfated saccharides can be used to downregulate inflammation processes. We have designed and synthesized new sulfated compounds based on small and biocompatible carbohydrates that are able to cross the BBB. A suitable protected donor and acceptor, obtained from a unique precursor, have been stereoselectively glycosylated to give an orthogonally protected cellobiose disaccharide. Selective deprotection and sulfation allowed the syntheses of four differentially sulfated disaccharides, which have been characterized by NMR, HRMS and MS/MS. Together with their partially protected precursors, the new compounds were tested on HEK-TLR4 cells. Our results show the potential of small oligosaccharides to modulate TLR4 activity, confirming the need for sulfation and the key role of the 6-sulfate groups to trigger TLR4 signalization.

Citation

Rachid Naïtaleb, Agnès Denys, Fabrice Allain, Jérôme Ausseil, Sylvestre Toumieux, José Kovensky. Synthesis of new sulfated disaccharides for the modulation of TLR4-dependent inflammation. Organic & biomolecular chemistry. 2021 May 21;19(19):4346-4351