Did you know that there are certain cells in our body which can detect bitterness? They’re found not just in the mouth but also in other parts of our body, for example, the airways. If these cells get triggered, then the lung passages open up – which could be used to treat illnesses like asthma or COPD. Recently, a research group came out with a strong and specific kind of compound that is likely to make it easier to create this type of treatment.
TAS2R14 is one of the 25 different types of taste receptors known to be found in different parts of your body that are not in your mouth. But, scientists aren’t sure how this receptor looks and what chemical activates it. Flufenamic acid, which is a medicine used to reduce inflammation, has been found to be able to bind with and make TAS2R14s work.
Scientists had difficulty inventing a better ligand, because the compounds they were working with weren’t very effective and didn’t look similar. But Masha Niv, Peter Gmeiner and their team got more successful when they used flufenamic acid as the starting point for their design. Now, their goal is to further extend this work and make an even better TAS2R14 ligand.
The researchers had previously discovered certain structures that can make a substance more powerful. To find out if this was true, they used an assay that looks at how active receptors are in cells. When they tried making some improvements to what they already had, they found that replacing the phenyl ring with a 2-aminopyrimidine and using tetrazole in place of carboxylic acid made their substance much stronger. The new ligand ended up being six times more potent than flufenamic acid – which means you need less of it to get the same effect as an NSAID.
Researchers have discovered a molecule that only targets the TAS2R14 bitter taste receptor. This means it’s very specific and won’t affect any of the other non-bitter receptors in our body, making it less likely to cause any side effects. Furthermore, this new discovery will help scientists learn more about how the bitter tastebud works which can be used to develop cures and medications for related issues.
The article “Discovery of 2-Aminopyrimidines as Potent Agonists for the Bitter Taste Receptor TAS2R14” was published in the Journal of Medicinal Chemistry, and was funded by the German Research Foundation. The authors of this study are Lukas Waterloo, Harald Hübner, Fabrizio Fierro, Tara Pfeiffer, Regine Brox, Stefan Löber, Dorothee Weikert, Masha Y. Niv and Peter Gmeiner.
