Consistent Bioactive Conformation of the Neu5Acα(2→3)Gal Epitope Upon Lectin Binding

Binding Epitopes of Gangliosides to their Neuronal Receptor, Myelin‐Associated Glycoprotein, from Saturation Transfer Difference NMR

“…Based on trNOE data and homology modeling, in the accompanying paper Ernst et al have devised a binding mode for 3 to MAG that is in agreement with the STD NMR data presented here. [16] Combination of these NMR-based methods and modeling shows the clear advantage of arriving at validated binding modes. The relative orientation of the pharmacophoric groups of these natural ligands will help to validate homology models of MAG and will lead to new, rationally designed inhibitors.…”

“…[13][14][15] Trisaccharide Siaa- (3), are fragments of GQ1ba, whereas the trisaccharide SiaaA C H T U N G T R E N N U N G (2!3) GalbA C H T U N G T R E N N U N G (1!3)Gal (1) is a close mimetic. [16] For reference purposes, the commercially available sialyllactose SiaaA C H T U N G T R E N N U N G (2!3) GalbA C H T U N G T R E N N U N G (1!4)Glc was also included in the study to obtain its K D value. Understanding the detailed binding mechanisms is essential for developing efficient inhibitors of this interaction.…”

From the Ganglioside GQ1b? to Glycomimetic Antagonists of the Myelin-Associated Glycoprotein (MAG)

“…In addition, the carboxylates of the two Neu5Ac moieties are involved in salt bridges and the C(9)-OH of the α(2-3)-linked Neu5Ac is forming a relevant hydrogen bond. [25] A verification of these findings by docking studies to a homology model of MAG [29,30] revealed the corresponding amino acids forming the binding site (Figs 3 and 6). Based on this information, a rational approach for the design of MAG antagonists was envisaged.…”

“…[29,30] The ligands were first manually docked to the binding pocket of the MAG model using the salt bridge to Arg118 and the hydrogen bond of the 9-OH to the backbone carbonyl of Phe129 as anchor points. Next, the protein-ligand complex was minimized in aqueous solution and then subjected to a molecular-dynamics equilibration protocol.…”

Carbohydrate Mimics and Lectins: A Source of New Drugs and Therapeutic Opportunities

“…If X-ray structures are not available, homology models can be generated. 28 Although oligosaccharides are relatively flexible molecules, if compared to other macromolecules, certain glycans have highly favoured conformations. 29 In particular, vicinal branching appears to impart a significant conformational restriction, as seen for instance in gangliosides 30 and in the Lewis determinants.…”