Stereoselective innovative synthesis and biological evaluation of new real carba analogues of minimal epitope Manα(1,2)Man as DC-SIGN inhibitors

Abstract : Antagonists of the C-type lectin DC-SIGN are promising therapeutic agents against viruses and bacteria. The development of glycomimetic ligands for DC-SIGN has so far proved to be challenging, since this membrane-protein presents four carbohydrate-binding domains (CRD) that specifically recognize mannose and fucose. In the recent past, we were able to develop inhibitors mimicking the minimal natural epitope Mana(1,2) Man using a mannoside with conformationally restricted dimethyl cycloexandicarboxylate-based aglycons designed to exploit the high enzymatic stability and to generate multivalent or solid supported systems as potent lectin ligands. Herein we describe the innovative synthesis of a different class of pseudodisaccharides, mimics of the natural Mana(1,2) Man moiety, characterized by the presence of a real D-carbamannose unit instead of a simpler mimic structure. Their chemical synthesis and biological activity using an SPR inhibition assay are reported. These pseudodisaccharides display inhibition values similar to those of the natural disaccharide Mana(1,2) Man, with a good affinity for DC-SIGN and can be considered as possible candidates for further structural modifications towards improved inhibitors.
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RSC Advances, Royal Society of Chemistry, 2016, 6 (92), pp.89578 - 89584. 〈10.1039/c6ra20401e〉
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Soumis le : mercredi 11 janvier 2017 - 08:53:39
Dernière modification le : lundi 19 février 2018 - 14:34:03

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Vittorio Bordoni, Vanessa Porkolab, Sara Sattin, Michel Thépaut, Ileana Frau, et al.. Stereoselective innovative synthesis and biological evaluation of new real carba analogues of minimal epitope Manα(1,2)Man as DC-SIGN inhibitors. RSC Advances, Royal Society of Chemistry, 2016, 6 (92), pp.89578 - 89584. 〈10.1039/c6ra20401e〉. 〈hal-01431523〉

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