Heterocycles that show a great diversity are found in many lead compounds. They are the structures containing one or more heteroatoms such as oxygen, nitrogen, or sulphur. They can be aliphatic as well as aromatic. They possess the potential of interacting with binding sites through several binding forces.
The directional aspect is of importance in concern with hydrogen bonding. The orientation of the ring and the position of the heterocycle in the ring are crucial in determination of the interaction.
Methotrexate, a heterocycle, is an anti-cancer drug. It contains a ring system of diamino-pteridine, which interacts with the specific site for binding. The hydrogen bonding networks within the binding site that it is involved with are quite intricate. The heteroatom nitrogen is the site that binds with the targets. It acts an inhibitor to dihydrofolate by binding to its natural substrate.
The enzyme which is responsible for reduction of dihydrofolic acid to tetrahydrofolic acid is Dihydrofolate reductase. The Nicotinamide Adenine Dinucleotide Phosphate (NADPH) is used as an electron donor to bind with the substrate.
The enzyme catalyzes the process of transfer of hydride to dihydrofolate from NADPH. This is accompanied by a protonation for production of tetrahydrofolate by reduction along with oxidation of NADPH.