People with asthma or COPD might one day take advantage of new treatments that trigger bitter taste receptors.
Remarkably, bitter taste receptors are not simply discovered in the mouth but likewise in other parts of the body, such as the airways. When activated, these receptors can open lung passages, making them a possible target for dealing with asthma or chronic obstructive lung disease (COPD). In a recent study published in ACS Journal of Medicinal Chemistry, researchers have actually established a selective and effective substance that might lead the way for potential therapies.
Amongst the 25 various kinds of bitter taste receptors, the TAS2R14 subtype is among the most commonly distributed in tissues outside the mouth. Researchers doubt about the structure of the receptor, and they havent determined the specific compound or “ligand” in the body that triggers it. Nevertheless, a few synthetic substances, such as the nonsteroidal anti-inflammatory drug (NSAID) flufenamic acid, are known to bind to and activate TAS2R14s.
These compounds arent extremely powerful, and they do not have comparable structural features. These troubles make it challenging to create a better ligand. Masha Niv, Peter Gmeiner, and coworkers utilized flufenamic acid as a starting point to style and synthesize analogs with enhanced properties. Next, the group wished to extend that work to establish a set of even much better TAS2R14 ligands.
Surprisingly, bitter taste receptors are not just found in the mouth but also in other parts of the body, such as the air passages. Amongst the 25 different types of bitter taste receptors, the TAS2R14 subtype is one of the most widely dispersed in tissues outside the mouth. Researchers are unpredictable about the structure of the receptor, and they have not determined the particular substance or “ligand” in the body that activates it.
Building on their earlier findings that specific kinds of structures enhanced potency, the researchers made several new variations. They checked these substances in a cell-based assay that determines receptor activation. This approach revealed that replacing a phenyl ring with a 2-aminopyrimidine and substituting a tetrazole for a carboxylic acid group was a promising technique. One of the new ligands was 6 times more powerful than flufenamic acid, suggesting less of the substance was needed to produce a similar reaction as the NSAID.
This ligand was also highly selective for TAS2R14 compared to non-bitter taste receptors, which could possibly minimize side results. The brand-new substances will assist shed light on the structure, system, and physiological function of bitter taste receptors and guide the advancement of drug prospects to target them, the scientists say.
Recommendation: “Discovery of 2-Aminopyrimidines as Potent Agonists for the Bitter Taste Receptor TAS2R14” by Lukas Waterloo, Harald Hübner, Fabrizio Fierro, Tara Pfeiffer, Regine Brox, Stefan Löber, Dorothee Weikert, Masha Y. Niv and Peter Gmeiner, 27 February 2023, Journal of Medicinal Chemistry.DOI: 10.1021/ acs.jmedchem.2 c01997.
The authors acknowledge financing from the German Research Foundation.
