Use of specific T2R taste receptors to identify compounds that block bitter taste
AssigneeSenomyx, Inc.
InventorsAlexey Pronin, Judy Connor, Huixian Tang, Walter Keung, Guy Servant, Jon Adler, Shawn O'Connell, Paul Brust
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Abstract
Assays for identifying compounds that modulate, preferably inhibit bitter taste associated with the activation of hT2R4, hT2R44 and/or hT2R61 are provided. The compounds identified according to these assays should modulate, e.g., inhibit bitter taste associated with bitter tasting compounds including quinine, 6-nitrosaccharin, saccharin and/or denatonium. These compounds are useful additives for foods, beverages or medicinal preparationshaving a bitter taste.
Claims116
An assay method for identifying a compound which modulates hT2R4 associated bitter taste comprising:
- (i) screening a compound for its effect on quinine or a structurally related compound to induce activation of hT2R4 or a variant, fragment, ortholog, mutant or chimera of said receptor that is activated by quinine;
- and
- (ii) determining whether said compound modulates bitter taste based on its effect on the activation of said receptor by quinine or a structurally related compound.
A method for identifying a compound that modulates hT2R4 bitter taste comprising:
- (i) obtaining a cell line or cell membrane that expresses a hT2R4 protein, variant, ortholog, chimera or fragment that is and optionally expresses a G protein;
- (ii) contacting said cell line with quinine or a related compound that activates hT2R4;
- (ii) contacting said cell line with at least one compound that is to be screened for its possible effect on bitter taste;
- and
- (iii) identifying whether said compound modulates bitter taste based on its effect on the activation of said protein, variant, ortholog, chimera or fragment by quinine or a related compound.
An assay method for identifying a compound which particularly modulates hT2R61 associated bitter taste comprising:
- (i) screening a compound for its effect on the activation of hT2R61, or a variant, fragment, ortholog, mutant or chimera of said receptor which specifically binds 6-nitrosaccharin, saccharin or a related compound;
- and
- (ii) determining whether said compound modulates hT2R61 associated bitter taste based on its effect on the activation of said receptor by 6-nitrosaccharin, saccharin or a structurally related compound.
A method for identifying a compound that modulates hT2R61 associated bitter taste comprising:
- (i) obtaining a cell line or cell membrane that expresses hT2R61 protein, variant, ortholog, chimera, or fragment that is involved in bitter taste and optionally contains an endogenous or exogenous G protein:
- (ii) contacting said cell line with 6-nitrosaccharin or a related compound that activates hT2R61;
- (iii) contacting said cell line with at least one compound that is to be screened for its possible effect on bitter taste;
- and
- (iv) identifying whether said compound modulates bitter taste based on its effect on the activation said hT2R61 protein, variant or fragment by 6-nitrosaccharin or a structurally related compound.
An assay method for identifying a compound which particularly modulates hT2R44 associated bitter taste comprising:
- (i) screening a compound for its effect on the activation of hT2R44, or a variant, fragment, chimera, ortholog, or mutant of said receptor by denatonium and/or 6-nitrosaccharin;
- and
- (ii) determining whether said compound modulates hT2R44 associated bitter taste based on its ability to modulate the activation of said receptor by denatonium and/or 6-nitrosaccharin or a structurally related compound.
A method for identifying a compound that modulates hT2R44 associated bitter taste comprising:
- (i) obtaining a cell line or cell membrane that expresses a hT2R44 protein, variant, ortholog, chimera or fragment that is involved in bitter taste and optionally contains an endogenous or exogenous G protein;
- (ii) contacting said cell line with denatonium or a related compound that activates hT2R44;
- (iii) contacting said cell line with at least one compound that is to be screened for its possible effect on bitter taste;
- and
- (iv) identifying whether said compound modulates bitter taste based on its effect on the activation of said T2R protein, variant or fragment by denatonium or a related compound.
Dependencies are inferred from the claim text.