Résumé
The interaction between glycoconjugates and lectins is characterized by a multivalent binding so-called "glycoside cluster effect". This feature has generated interest in developing suitable architectures to decipher ligand-receptor interactions. In this context, the 300 kDa cation-independent mannose-6-phosphate receptor (M6P receptor or CI-MPR) plays a critical role in mediating ligand internalization and trafficking to endolysosomal compartments, making it a promising class of receptors for targeted drug delivery strategies.[1] CI-MPR contains two high-affinity M6P binding sites at domains 3 and 9, and its cellular uptake requires the formation of receptor dimers involving the simultaneous binding of two protein units. [2] Thus, multivalent ligands for CI-MPR must target multiple M6P binding pockets to induce internalization. One challenge in designing glycoconjugates for CI-MPR is to achieve a precise control of the spatial arrangement of carbohydrate ligands. Although large glycoconjugates, such as high-density glycopeptides, polymers, and dendrimers,[3] have been explored, they are unstructured highly flexible systems and are unable to project the sugar units in an optimal isotropic fashion around the central core. We herein address the question of how heterocyclic γ-peptide foldamers[4] can be used to control the distribution of the saccharide elements and potentiate efficient cell uptake of glycoconjugates.[5]