Structural Insights Into The Binding Of Sugar Receptors (Lectins) To A Synthetic Tricyclic Tn Mimetic And Its Glycopeptide Version

Cycloadduct 1 is a conformationally constrained mimetic of the tumor-associated Tn antigen. It maintains the C-4(1) conformation and the -O-glycosidic linkage of the natural epitopes. Due to its tricyclic structure, the anomeric linkage is constrained and its conformation frozen. Using saturation transfer difference NMR spectroscopy experiments, epitope mapping for binding by three lectins [i.e., from Erythrina cristagalli (ECL), human macrophages (MGL), and from Helix pomatia (HPA)] was carried out. Striking differences in the epitope viewed from the ligand's perspective were revealed by this comparison. Evidently, the structural change around the C-2 position has a major impact, if the contact pattern to the ligand is not mostly restricted to galacto configuration with the axial hydroxyl group at C-4, in combination with C-3/C-6. These measurements thus provide insights into actual contacts, which help predict applicability as an inhibitor for distinct lectins, and as an elicitor of specific antibodies.