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.
journal_name
Chem Biol Drug Desjournal_title
Chemical biology & drug designauthors
Karaman R,Nowak S,Di Pizio A,Kitaneh H,Abu-Jaish A,Meyerhof W,Niv MY,Behrens Mdoi
10.1111/cbdd.12734subject
Has Abstractpub_date
2016-07-01 00:00:00pages
66-75issue
1eissn
1747-0277issn
1747-0285journal_volume
88pub_type
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