BONDS AND ATTRACTIVE FORCES

How do drugs bind to their receptors?

Receptors are proteins or enzymes that are large and coated, while agonists or pharmacological agents are small. Thus the agonists will fit in a cavity within the protein. The shape of the cavity must be just right for the specific drug. This cavity must have 2 important attributes:

1. to recognize one molecule over another

2. to bind the agonist very tightly

In our armamentarium of drugs there are chemical analogs to natural transmitters, which can be recognized individually by receptors

How do receptors keep the transmitter tightly attached?

Via different kinds of bonds

• covalent bonds: sharing an orbit, very strong bond, unusual in pharmacology, permanent bond

• ionic bonds: more common, positive and negative charge interaction

• hydrogen bonds: oxygen is partially negative by an uneven distribution of electron cloud, while hydrogen has a little bit of a positive charge; although one H-bond is very weak, multiple H-bonds are strong, most common mechanism for drug:receptor interaction

• hydrophobic interactions: cyclic moieties (rings) usually don’t like water, so the hydrophobic particles will be attracted to each other instead of water

• van der Waals interactions: weak bond, essential for the molecules to be close enough for the electron clouds to intermingle with each other

Many drugs come from plants or plant extracts-- now however, the 3D structure of proteins can be utilized (thanks to the genome project) via computers, and synthetic molecules can be specifically created to bind to certain receptors. This was how HIV protease inhibitors were created.

Category: Pharmacology Notes