Cover Picture: Molecular Recognition of β-O-GlcNAc Glycopeptides by a Lectin-Like Receptor: Binding Modulation by the Underlying Ser or Thr Amino Acids (ChemBioChem 1/2011)



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The cover picture shows the binding of different β-O-GlcNAc derivatives to a synthetic lectin-like receptor. The study combined NMR experiments with extensive MD simulations in explicit water. Notably, the presence of a key hydrogen bond between the receptor and the OMe group of the β-O-GlcNAc-OMe derivative appears to be responsible for the high selectivity observed for this compound. In addition, to study the effect of the underlying amino acid on the binding, we prepared four β-O-GlcNAc model glycopeptides that include serine, threonine, and the non-natural α-methylserine and α-methylthreonine as underlying residues. While the serine-containing glycopeptide exhibited the highest affinity constant of the glycopeptides, the threonine derivative showed the lowest one. This low selectivity could have its origin in the difficulty of forming both specific hydrogen bonds and hydrophobic (CH–π) contacts. For further information, see the paper by J. M. Peregrina et al. on p. 110 ff.