# US 7,407,769 B2 · Method of identifying activity modulators of a polycystin-2L1 taste receptor polypeptide > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 7,407,769 B2 - Document ID: US7407769B2 - Status: Granted - Kind: B2 - Application number: 11/176,958 - Filed: 2005-07-06 - Published: 2007-01-11 - Granted: 2008-08-05 - Earliest claimed: 2005-07-06 - Assignees: The Regents of the University of California - Inventors: Charles Zuker; Angela L. Huang - Web page: https://patentgrep.com/patent/US7407769B2 ## CPC - G01N 33/566: using specific carrier or receptor proteins as ligand binding reagents {where possible specific carrier or receptor proteins are classified with their target compounds} - C07K 14/705: Receptors; Cell surface antigens; Cell surface determinants {(tumour specific antigens C07K14/4748)} - G01N 33/5008: {for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics} - G01N 33/502: {for testing non-proliferative effects} - G01N 33/5044: {involving specific cell types} - G01N 33/6872: {Intracellular protein regulatory factors and their receptors, e.g. including ion channels} - A01K 2217/05: Animals comprising random inserted nucleic acids (transgenic) - A01K 2217/075: inducing loss of function, i.e. knock out - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - A01K: ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS ## Abstract Taste receptor polycystin-2L1 is provided. Methods and systems for screening for tastants and receptor modulators are provided. Knock out and transgenic animals, methods of detecting polymorphisms, and methods of correcting taste defects are also provided. ## Claims ### Claim 1 A method of identifying a compound that binds to or modulates an activity of a polycystin-2L1 taste receptor polypeptide, the method comprising: (a.) contacting a biological or biochemical sample comprising the polycystin-2L1 taste receptor polypeptide with a test compound; and, (b.) detecting binding of the test compound to the polycystin-2L1 taste receptor polypeptide, or modulation of the activity of the polypeptide by the test compound, thereby identifying the compound which binds to or modulates the activity of the polycystin-2L1 taste receptor polypeptide. ### Claim 2 (depends on 1) The method of claim 1, wherein (a.) comprises contacting one or more biological sample comprising one or more polycystin-2L1 taste receptor polypeptides with a plurality of test compounds and wherein (b.) comprises detecting binding of the test compounds to the polycystin-2L1 taste receptor polypeptides, or modulation of the activity of the polypeptides by the test compounds, thereby identifying one or more compounds that binds to or modulates the activity of the polycystin-2L1 taste receptor polypeptides. ### Claim 3 (depends on 2) The method of claim 2, wherein the plurality of test compounds comprises a plurality of pre-screened compounds. ### Claim 4 (depends on 1) The method of claim 1, wherein the test compound is selected from the group consisting of: naturally occurring compounds, ions, sour tastants, small organic molecules, peptides, peptide mimetics, a weak acid, CO2, acetic acid, a specific blocker of carbonic anhydrase, and MK-417. ### Claim 5 (depends on 1) The method of claim 1, wherein the test compound enhances an activity of the polycystin-2L1 taste receptor polypeptide. ### Claim 6 (depends on 1) The method of claim 1, wherein the test compound potentiates an activity of the polycystin-2L1 taste receptor polypeptide. ### Claim 7 (depends on 1) The method of claim 1, wherein the test compound inhibits or blocks an activity of the polycystin-2L1 taste receptor polypeptide. ### Claim 8 (depends on 1) The method of claim 1, wherein the polycystin-2L1 taste receptor polypeptide is a human polycystin-2L1 taste receptor polypeptide. ### Claim 9 (depends on 1) The method of claim 1, wherein the polycystin-2L1 taste receptor polypeptide is a murine polycystin-2L1 taste receptor polypeptide. ### Claim 10 (depends on 1) The method of claim 1, wherein the polycystin-2L1 taste receptor polypeptide is a polycystin-2L1 taste receptor polypeptide from a domesticated or livestock animal. ### Claim 11 (depends on 1) The method of claim 1, wherein step (b.) includes detecting binding between the polycystin-2L1 taste receptor polypeptide and a moiety selected from the group consisting of: a potentiator of the polycystin-2L1 taste receptor polypeptide, an antagonist of the polycystin-2L1 taste receptor polypeptide, an agonist of the polycystin-2L1 taste receptor polypeptide, an inverse agonist of the polycystin-2L1 taste receptor polypeptide, a ligand that specifically binds to the polycystin-2L1 taste receptor polypeptide, and an antibody that specifically binds to the polycystin-2L1 taste receptor polypeptide. ### Claim 12 (depends on 1) The method of claim 1, wherein step (b.) includes in situ or in vivo detection of the polycystin-2L1 taste receptor polypeptide. ### Claim 13 (depends on 1) The method of claim 1, wherein step (b.) includes detecting a signal resulting from the activity of the polycystin-2L1 taste receptor polypeptide. ### Claim 14 (depends on 13) The method of claim 13, wherein the signal is a conformation-dependent signal, wherein a conformation of the polycystin-2L1 taste receptor polypeptide is modified by binding of the test compound to the polycystin-2L1 taste receptor polypeptide. ### Claim 15 (depends on 1) The method of claim 1, wherein the biological sample comprises or is derived from a cell that expresses the polycystin-2L1 taste receptor polypeptide. ### Claim 16 (depends on 15) The method of claim 15, wherein detecting binding of the test compound to the polycystin-2L1 taste receptor polypeptide, or activity of the test compound on the polycystin-2L1 taste receptor polypeptide comprises detecting one or more of: H+ flux, Na+ flux, Ca2+ flux, ion flux, depolarization of the cell, cell membrane voltage changes, cell membrane conductivity changes, a kinase activity triggered upon binding of a compound to the polycystin-2L1 taste receptor polypeptide, generation, breakdown or binding of a phorbol ester by the polycystin-2L1 taste receptor polypeptide, binding of diacylglycerol or other lipids by the polycystin-2L1 taste receptor polypeptide, cAMP activity, cGMP activity, GTPgammaS binding, phospholipase C activity, activity of an enzyme involved in cellular ionic balance, binding of polycystin-2L1 to another PKD protein, or a transcriptional reporter activity. ### Claim 17 (depends on 1) The method of claim 1, further comprising recombinantly expressing a PKD2L1 gene in a recombinant cell, wherein the biological sample is derived from the recombinant cell. ### Claim 18 (depends on 17) The method of claim 17, wherein the PKD2L1 gene is heterologous to the recombinant cell. ### Claim 19 (depends on 18) The method of claim 18, wherein the cell is a human, rodent or insect cell, and wherein the cell is a cell in culture or a primary cell. ### Claim 20 (depends on 17) The method of claim 17, wherein the cell is a taste bud or kidney cell, or wherein the cell is a cell derived from a taste bud or kidney cell. ### Claim 21 (depends on 1) The method of claim 1, wherein the polycystin-2L1 taste receptor polypeptide is incorporated into a biosensor. ### Claim 22 (depends on 21) The method of claim 21, wherein the biosensor comprises a Chem-FET. ### Claim 23 A system for detecting compounds that bind to or modulate an activity of a polycystin-2L1 taste receptor polypeptide, the system comprising: (a.) a biological sample comprising the polycystin-2L1 taste receptor polypeptide; (b.) a source of a plurality of test compounds; and, (c.) a detector that detects binding of one or more of the test compounds to the polycystin-2L1 taste receptor polypeptide, or modulation of the activity of the polypeptide by one or more of the test compounds, thereby identifying a putative tastant compound that binds to or modulates the activity of the polycystin-2L1 taste receptor polypeptide. ### Claim 24 (depends on 23) The system of claim 23, wherein the biological sample comprises a cell comprising a heterologous gene encoding the polycystin-2L1 taste receptor polypeptide. ### Claim 25 (depends on 24) The system of claim 24, wherein the cell is selected from the group consisting of: a mammalian cell, an insect cell, a Xenopus cell, and a taste receptor cell. ### Claim 26 (depends on 23) The system of claim 23, wherein the source of test compounds comprises a library of tastant compounds. ### Claim 27 (depends on 23) The system of claim 23, wherein the source of test compounds comprises a pre-screened library of compounds. ### Claim 28 (depends on 23) The system of claim 23, wherein the detector comprises a patch clamp device or an optical detection device. ### Claim 29 (depends on 23) The system of claim 23, wherein the detector comprises a flourescence detector that detects FRET, changes in membrane potential or flow of a dye into or out of the cell.