alpha-N-Linked glycopeptides: conformational analysis and bioactivity as lectin ligands

Natural N-glycosylation involves a beta-anomeric linkage connecting the sugar to one asparagine residue of the protein. We herein report NMR- and modelling-based data on glycomimetics containing alpha-glycosidic linkages. The bioactivity of alpha-Gal-containing glycopeptides has been documented by revealing binding to two plant lectins, i.e. a potent beta-trefoil toxin (Viscum album agglutinin) and beta-sandwich lectin (Erythrina corallodendron agglutinin), by NMR protocols. Docking provided insights into the 3D structures of the resulting complexes. These results provide the basis to introduce alpha-substituted neoglycopeptides to the toolbox of scaffold for the design of potent lectin inhibitors.