Dehydron

A dehydron is an intramolecular hydrogen bond

Hydrogen bond

A hydrogen bond is the attractive interaction of a hydrogen atom with an electronegative atom, like nitrogen, oxygen or fluorine . The hydrogen must be covalently bonded to another electronegative atom to create the bond...

 incompletely shielded from water attack

Water

Water is an ubiquitous chemical substance that is composed of hydrogen and oxygen and is essential for all known forms of life.In typical usage, water refers only to its liquid form or state, but the substance also has a solid state, ice, and a gaseous state, water vapor or steam. Water covers 71%...

, with a propensity to promote its own dehydration

Dehydration

Dehydration is defined as excessive loss of body water. It is literally the removal of water from an object. In physiological terms, it entails a relative deficiency of water molecules in relation to other dissolved solutes...

. Dehydrons constitute a special kind of packing defect in soluble proteins and were named and characterized by Argentine-born American scientist Ariel Fernandez, from Rice University, and his coworkers Ridgway Scott, Stephen Berry and Harold Scheraga.

Dehydrons are partially dehydrated amide

Amide

In chemistry, an amide is usually an organic compound that contains the functional group consisting of an acyl group linked to a nitrogen atom . The term refers both to a class of compounds and a functional group within those compounds...

-carbonyl

Carbonyl

In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom : C=O.The term carbonyl can also refer to carbon monoxide as a ligand in an inorganic or organometallic complex In organic chemistry, a carbonyl group is a functional group...

 hydrogen bonds that result from an incomplete clustering of side-chain nonpolar groups that "wrap" the polar

Chemical polarity

In chemistry, polarity refers to a separation of electric charge leading to a molecule having an electric dipole. Polar molecules can bond together due to dipole–dipole intermolecular forces between one molecule with asymmetrical charge distribution and another molecule also with asymmetrical...

 pair within the protein structure

Protein structure

Proteins are an important class of biological macromolecules present in all biological organisms, made up of such elements as carbon, hydrogen, nitrogen, oxygen, and sulphur. All proteins are polymers of amino acids. According to their physical size, proteins are nanoparticles...

.

A dehydron is an intramolecular hydrogen bond

Hydrogen bond

A hydrogen bond is the attractive interaction of a hydrogen atom with an electronegative atom, like nitrogen, oxygen or fluorine . The hydrogen must be covalently bonded to another electronegative atom to create the bond...

 incompletely shielded from water attack

Water

Water is an ubiquitous chemical substance that is composed of hydrogen and oxygen and is essential for all known forms of life.In typical usage, water refers only to its liquid form or state, but the substance also has a solid state, ice, and a gaseous state, water vapor or steam. Water covers 71%...

, with a propensity to promote its own dehydration

Dehydration

Dehydration is defined as excessive loss of body water. It is literally the removal of water from an object. In physiological terms, it entails a relative deficiency of water molecules in relation to other dissolved solutes...

. Dehydrons constitute a special kind of packing defect in soluble proteins and were named and characterized by Argentine-born American scientist Ariel Fernandez, from Rice University, and his coworkers Ridgway Scott, Stephen Berry and Harold Scheraga.

Dehydrons are partially dehydrated amide

Amide

In chemistry, an amide is usually an organic compound that contains the functional group consisting of an acyl group linked to a nitrogen atom . The term refers both to a class of compounds and a functional group within those compounds...

-carbonyl

Carbonyl

In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom : C=O.The term carbonyl can also refer to carbon monoxide as a ligand in an inorganic or organometallic complex In organic chemistry, a carbonyl group is a functional group...

 hydrogen bonds that result from an incomplete clustering of side-chain nonpolar groups that "wrap" the polar

Chemical polarity

In chemistry, polarity refers to a separation of electric charge leading to a molecule having an electric dipole. Polar molecules can bond together due to dipole–dipole intermolecular forces between one molecule with asymmetrical charge distribution and another molecule also with asymmetrical...

 pair within the protein structure

Protein structure

Proteins are an important class of biological macromolecules present in all biological organisms, made up of such elements as carbon, hydrogen, nitrogen, oxygen, and sulphur. All proteins are polymers of amino acids. According to their physical size, proteins are nanoparticles...

. Dehydrons are sticky

Sticky

Stickiness or the quality of being sticky can refer to several things:* the physical phenomena of adhesion and cohesion* the defining physico-chemical property of glue* Sticky * Sticky...

, since they promote the removal of surrounding water

Water

Water is an ubiquitous chemical substance that is composed of hydrogen and oxygen and is essential for all known forms of life.In typical usage, water refers only to its liquid form or state, but the substance also has a solid state, ice, and a gaseous state, water vapor or steam. Water covers 71%...

 through protein associations and/or ligand binding

Ligand

In chemistry, a ligand is either an atom, ion, or molecule that binds to a central metal-atom to produce a coordination complex. The bonding between the metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The metal-ligand bonding ranges from covalent...

. This further dehydration enhances the electrostatic interaction

Interaction

Interaction is a kind of action that occurs as two or more objects have an effect upon one another. The idea of a two-way effect is essential in the concept of interaction, as opposed to a one-way causal effect...

 between the amide

Amide

In chemistry, an amide is usually an organic compound that contains the functional group consisting of an acyl group linked to a nitrogen atom . The term refers both to a class of compounds and a functional group within those compounds...

 and carbonyl

Carbonyl

In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom : C=O.The term carbonyl can also refer to carbon monoxide as a ligand in an inorganic or organometallic complex In organic chemistry, a carbonyl group is a functional group...

 groups by de-shielding their partial charges

Charge

-In mathematics, science, and technology:* Charge , the air and/or fuel mixture being fed to an internal combustion engine* Charge , the susceptibility of a body to one of the fundamental forces...

. Furthermore, the dehydration stabilizes the hydrogen bond

Hydrogen bond

A hydrogen bond is the attractive interaction of a hydrogen atom with an electronegative atom, like nitrogen, oxygen or fluorine . The hydrogen must be covalently bonded to another electronegative atom to create the bond...

 by destabilizing the nonbonded state that consists of dehydrated isolated charges

Charge

-In mathematics, science, and technology:* Charge , the air and/or fuel mixture being fed to an internal combustion engine* Charge , the susceptibility of a body to one of the fundamental forces...

. Hence, the name dehydron makes reference to the tendency to promote its dehydration

Dehydration

Dehydration is defined as excessive loss of body water. It is literally the removal of water from an object. In physiological terms, it entails a relative deficiency of water molecules in relation to other dissolved solutes...

, a process both energetically

Energy

In physics, energy is a scalar physical quantity that describes the amount of work that can be performed by a force, an attribute of objects and systems that is subject to a conservation law...

 and thermodynamically

Thermodynamics

In physics, thermodynamics is the study of the conversion of energy into work and heat and its relation to macroscopic variables such as temperature, volume and pressure...

 favored. Thus, dehydrons are markers for protein interactivity

Protein

Proteins are organic compounds made of amino acids arranged in a linear chain and folded into a globular form. The amino acids in a polymer chain are joined together by the peptide bonds between the carboxyl and amino groups of adjacent amino acid residues...

, and hence functional indicators, and may possibly serve as drug targets

Drug

A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...

.

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))