Cover Picture: Carbohydrate-Lectin Interactions: An Unexpected Contribution to Affinity (ChemBioChem 6/2017)

The cover picture shows the bacterial adhesin PapG-II. Its expression has been correlated with the onset of pyelonephritis in humans, a potentially life-threatening condition. It was envisaged that blocking PapG-II interactions to prevent bacterial adhesion might offer a viable therapeutic alternative to conventional antibiotic treatment. During our search for potent PapG-II antagonists, we observed an increase in binding energy when tetrasaccharide GalNAc(β1–3)Gal(α1–4)Gal(β1–4)Glc, the natural ligand of PapG-II in human kidneys, was elongated to hexasaccharide Neu5Ac(α2–3)Gal(β1–3)GalNAc(β1–3)Gal(α1–4)Gal(β1–4)Glc, even though the additional Neu5Ac(α2–3)Gal extension was not observed to be in direct contact with the lectin. Thermodynamic studies suggest that the increased affinity results from partial desolvation of nonbinding regions of the hexasaccharide, effectively knocking water molecules out of the outer hydration layers. Our results suggest a general mechanism for modulating carbohydrate–protein interactions by utilizing nonbinding regions of the ligand. Cover design: Christoph Sager based on an idea by B.E. Background image: katatonia82/Shutterstock, Inc. More information can be found in the full paper by B. Ernst et al. on page 539 in Issue 6, 2017 (DOI: 10.1002/cbic.201600615).