Drug Targets at the Molecular Level

The main molecular targets for drugs are proteins (mainly enzymes, receptors, and transport proteins) and nucleic acids (DNA and RNA). These The main molecular targets for drugs are proteins (mainly enzymes, receptors, and transport proteins) and nucleic acids (DNA and RNA). These are large molecules ( macromolecules ) that have molecular weights measured in the order of several thousand atomic mass units. They are much bigger than the typical drug, which has a molecular weight in the order of a few hundred atomic mass units. The interaction of a drug with a macromolecular target involves a process known as binding. There is usually a specific area of the macromolecule where this takes place, known as the binding site. Typically, this takes the form of a hollow or canyon on the surface of the macromolecule allowing the drug to sink into the body of the larger molecule. Some drugs react with the binding site and become permanently attached via a covalent bond that has a bond strength of 200-400 kJ mol−1 . However, most drugs interact through weaker forms of interaction known as intermolecular bonds. These include electrostatic or ionic bonds, hydrogen bonds, van der Waals interactions, dipole–dipole interactions, and hydrophobic interactions. (It is also possible for these interactions to take place within a molecule, in which case they are called intramolecular bonds) None of these bonds is as strong as the covalent bonds that make up the skeleton of a molecule, and so they can be formed and then broken again. This means that an equilibrium takes place between the drug being bound and unbound to its target. The binding forces are strong enough to hold the drug for a certain period of time to let it have an effect on the target, but weak enough to allow the drug to depart once it has done its job. The length of time the drug remains at its target will then depend on the number of intermolecular bonds involved in holding it there. Drugs that have a large number of interactions are likely to remain bound longer than those that have only a few. The relative strength of the different intermolecular binding forces is also an important factor. Functional groups present in the drug can be important in forming intermolecular bonds with the target binding site. If they do so, they are called binding groups. However, the carbon skeleton of the drug also plays an important role in binding the drug to its target through van der Waals interactions. As far as the target binding site is concerned, it too contains functional groups and carbon skeletons which can form intermolecular bonds with ‘visiting’ drugs. The specific regions where this takes place are known as binding regions. The study of how drugs interact with their targets through binding interactions and produce a pharmacological effect is known as pharmacodynamics.