Bitter taste receptor T2R14: Application of functional in-vitro system for finding novel agonists

Taste receptors for bitter substances (T2Rs) belong to the family of G-protein coupled receptors. There are 25 known T2Rs in humans responsible for bitter taste perception. Bitter taste receptor (T2R14) is one of the human bitter taste receptors, recognizing an enormous variety of structurally different molecules, including natural and synthetic bitter compounds. T2R14 expressed not only in the oral cavity, but also in other tissues and involved in others physiological processes outside the tongue, and there is a growing interest in their potential role in health and diseases.

We established a functional T2R14 cell-based system that detects the receptor-ligand complex activation by measuring the formation of myo-Inositol 1 phosphate (IP1), a downstream metabolite in the Gαq signal transduction pathway.

Through computational structure-based screening and experimental approaches, we confirmed one novel T2R14 activator AMD-DB2. This compound did not show high similarly based on chemical properties to other known T2R14 agonists. Hence, this molecule can be considered as a novel T2R14 agonist. Predicted docked poses of AMD-DB2 underlined the importance of structural features in both the ligand and the receptor for ligand-receptor activity.