Dehydron 5754352 199901225 2008-03-21T20:08:52Z Arifer 1674423 A '''dehydron''' is an intramolecular [[hydrogen bond]] incompletely shielded from [[water|water attack]], with a propensity to promote its own [[dehydration]]. Dehydrons constitute a special kind of packing defect in soluble [[proteins]] and were named and characterized by Argentine-born American scientist [http://www.owlnet.rice.edu/~arifer/ Ariel Fernandez], from [http://www.rice.edu Rice University], and his coworkers [http://www.cs.uchicago.edu/~ridg/ Ridgway Scott], [http://chemistry.uchicago.edu/fac/berry.shtml Stephen Berry] and [http://www.chem.cornell.edu/has5 Harold Scheraga]. Dehydrons are partially [[dehydrated]] [[amide]]-[[carbonyl]] [[hydrogen bonds]] that result from an incomplete clustering of side-chain [[nonpolar]] groups that "wrap" the [[Chemical polarity|polar]] pair within the [[protein structure]]. Dehydrons are [[sticky]], since they promote the removal of [[water|surrounding water]] through [[proteins|protein associations]] and/or [[ligand|ligand binding]]. This further dehydration enhances the [[electrostatic]] [[interaction]] between the [[amide]] and [[carbonyl]] groups by de-[[shielding]] their [[charge|partial charges]]. Furthermore, the dehydration stabilizes the [[hydrogen bond]] by destabilizing the [[nonbonded interactions|nonbonded state]] that consists of dehydrated [[charge|isolated charges]]. Hence, the name dehydron makes reference to the tendency to promote its [[dehydration]], a process both [[energy|energetically]] and [[thermodynamics|thermodynamically]] favored. Thus, dehydrons are markers for [[protein|protein interactivity]], and hence functional indicators, and may possibly serve as [[drug|drug targets]]. Dehydron patterns are not conserved across proteins with common ancestry (paralogs), hence dehydrons constitute structural singularities that have been targeted by drug ligands to achieve higher specificity and ultimately, to control side effects. This observation prompted researchers to introduce the design concept of "drug as dehydron wrapper", and heralded the advent of a novel approach to drug development, the so-called "wrapping technology". The design concept of dehydron as a selectivity-promoting feature to reduce side effects in drugs has been recently highlighted: * Crunkhorn, S.: Anticancer Drugs: Redesigning kinase inhibitors. Nature Reviews Drug Discovery 7, 120-121 (2008) * Demetri, G: Structural reengineering of imatinib to decrease cardiac risk in cancer therapy. Journal of Clinical Investigation 117, 3650-3653 (2007)) ==References:== * Fernandez, A. and Scott, L. R. Phys. Rev. Lett. 91, 08102 (2003). * Fernandez, A. and Berry, R. S. Proc. Natl. Acad. Sci. USA 101, 13460-13465 (2004). * Fernandez, A. Nature Biotechnology 22, 1081-1085 (2004). * Fernandez A, et al. Cancer Research 67, 4028-4033 (2007) Priority Report. * Chen, J. P., Zhang, X. and Fernandez, A. Bioinformatics 23, 563-572 (2007) * Crespo, A. and Fernandez, A. Drug Discovery Today 12, 917-923 (2007) * Fernandez, A. et al. Journal of Clinical Investigation 117, 4044-4054 (2007) [[Category:Hydrogen physics]]