Fucosylated ubiquitin and orthogonally glycosylated mutant A28C: conceptually new ligands for lectin (BambL).

Two orthogonal, metal free click reactions, enabled to glycosylate ubiquitin and its mutant A28C forming two protein scaffolds with high affinity for BambL, a lectin from the human pathogen . A new fucoside analogue, with high affinity with BambL, firstly synthetized and co-crystallized with the protein target, provided the insights for sugar determinants grafting onto ubiquitin. Three ubiquitin-based glycosides were thus assembled. , presented several copies of the fucoside analogue, with proper geometry for multivalent effect; , displayed one thio-rhamnose, known for its ability to tuning the immunological response; finally, , included both multiple fucoside analogs and the rhamnose residue. and ligands proved high affinity for BambL and unprecedented immune modulatory properties towards macrophages activation.