Abstract

DESIGN OF PRODRUGS TO REPLACE COMMONLY USED DRUGS HAVING BITTER SENSATION

Rafik Karaman*

Abstract

As the role of taste receptors in food-intake regulation is being unraveled, agonists and antagonists of bitter taste receptors will have additional important roles in modulating food intake and metabolism. Obesity has reached epidemic proportions in many countries around the world. Modulators of food intake and appetite are therefore of immense importance to health systems worldwide. Since bitter taste receptors are present in the mammalian gastrointestinal system, the ability to control interactions between these receptors and the corresponding bitter compounds might therefore have even more direct consequences for food intake and metabolism. Replacing commonly used bitter pediatric medicines with bitterless prodrugs that upon in vivo conversion provide the bitter active drugs and improving the molecular understanding of bitterness are being currently the most important tasks for many chemists and biochemists alike. The combination of the biological, chemical and computational expertise will without any doubt lead to better understanding of the structure-function relationships of bitter taste receptors and develop candidates for bitter taste inhibition. Such inhibitors will be of great value for pharmaceutical and food industries, since they will be able to eliminate the aversive taste of medicine and foods and should therefore result in better patient compliance in taking medicines, as well as increased consumer acceptance of healthy, but bitter vegetables and fruits.

Keywords: Bitter taste, Bitter taste receptors, DFT calculations, Molecular mechanics calculation, Quantum mechanics calculations, Enzyme models.