Field of Research: Chemical Biology
Name of author) (s): Rafik Karaman, Stefanie Nowak, Antonella Di Pizio, Hothaifa Kitaneh, Alaa Abu‐Jaish, Wolfgang Meyerhof, Masha Y. Niv and Maik Behrens
Title of published work: “Probing the binding pocket of the broadly tuned human bitter taste receptor TAS2R14 by chemical modification of cognate agonists”
Name of Journal: Chemical Biology & Drug Design
Year: 2016
Volume: Published online DOI: 10.1111/cbdd.12734
Pages: N/A
Publisher: John Wiley and Sons
Abstract:
Sensing potentially harmful bitter substances in the oral cavity is achieved by a group of ∼25 receptors, named TAS2Rs, which are expressed in specialized sensory cells and recognize individual but overlapping sets of bitter compounds. The receptors differ in their tuning breadths ranging from narrowly to broadly tuned receptors. One of the most broadly tuned human bitter taste receptors is the TAS2R14 recognizing an enormous variety of chemically diverse synthetic and natural bitter compounds, including numerous medicinal drugs. This suggests that this receptor possesses a large readily accessible ligand binding pocket. To allow probing the accessibility and size of the ligand binding pocket, we chemically modified cognate agonists and tested receptor responses in functional assays. The addition of large functional groups to agonists was usually possible without abolishing agonistic activity. The newly synthesized agonist derivatives were modeled in the binding site of the receptor, providing comparison to the mother substances and rationalization of the in vitro activities of this series of compounds.
Keywords:
TAS2R binding pocket; bitter taste receptor; chemical ligand design; functional calcium imaging; in silico homology modeling.
Contact author (s):
Name: Rafik Karaman, PhD.
Address: Al Quds University, Faculty of Pharmacy
E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.
