A dehydron is an intramolecular hydrogen bond incompletely shielded from water attack, with a propensity to promote its own dehydration. They constitute a special kind of packing defect in proteins and were named and characterized by Ariel Fernandez and his co-workers Ridgway Scott, Stephen Berry, and Harold Scheraga.
Dehydrons are partially dehydrated amide-carbonyl hydrogen bonds that result from an incomplete clustering of side-chain nonpolar groups that "wrap" the polar pair within the protein structure. Dehydrons promote the removal of surrounding water through protein associations or ligand binding. The exogenous dehydration enhances the electrostatic interaction between the amide and carbonyl groups by de-shielding their partial charges. Furthermore, the dehydration stabilizes the hydrogen bond by destabilizing the nonbonded state consisting of dehydrated isolated charges. Hence, the name dehydron makes reference to the tendency to promote its dehydration, a process both energetically and thermodynamically favored. Due to their dehydration propensity, dehydrons are markers for protein interactivity, hence functional indicators, and may serve as drug targets.
Dehydron patterns are not conserved across proteins with common ancestry (paralogs), hence dehydrons constitute structural singularities that may be targeted by drug ligands to control specificity in molecular therapy. This observation provides a novel approach to molecular targeted therapy, "wrapping technology".,
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