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AssigneeSenomyx, Inc.
InventorsMark Zoller, Xiaodong Li, Lena Staszewski, Shawn O'Connell, Sergey Zozulya, Jon Elliot Adler, Hong Xu, Fernando Echeverri
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The present invention relates to the discovery that the T1R receptors assemble to form functional taste receptors. Particularly, it has been discovered that co-expression of T1R1 and T1R3 results in a taste receptor that responds to umami taste stimuli, including monosodium glutamate. Also, it has been discovered that co-expression of the T1R2 and T1R3 receptors results in a taste receptor that responds to sweet taste stimuli including naturally occurring and artificial sweeteners. Also the present invention relates to the use of hetero-oligomeric taste receptors comprising T1R1/T1R3 and T1R2/T1R3 in assays to identify compounds that respectively respond to umami taste stimuli and sweet taste stimuli. Further, the invention relates to the constitutive of cell lines that stably or transiently co-express a combination of T1R1 and T1R3; or T1R2 and T1R3; under constitutive or inducible conditions. The use of these cells lines in cell-based assays to identify umami and sweet taste modulatory compounds is also provided, particularly high throughput screening assays that detect receptor activity by use of fluorometric imaging. Finally, the invention relates to the discovery that some compounds, e.g., lactisole, inhibit both the activities of human T1R2/T1R3 and T1R1/T1R3 receptors, and accordingly the sweet and umami taste, suggesting that these receptors may be the only sweet and umami receptors.
A receptor comprised of at least one T1R1 polypeptide (or a variant, fragment, or chimera of said T1R1 polypeptide) and/or at least one T1R3 polypeptide (or a variant, fragment, or chimera of said T1R3 polypeptide), wherein said receptor specifically binds to and/or is activated by umami taste stimuli.
A cell that expresses a receptor comprised of at least one T1R1 polypeptide (or a variant, fragment, or chimera of said T1R1 polypeptide) and/or at least one T1R3 polypeptide (or a variant, fragment, or chimera of said T1R3 polypeptide), wherein said receptor specifically binds to and/or is activated by umami taste stimuli.
A receptor comprised of at least one T1R2 polypeptide (or a variant, fragment, or chimera of said T1R2 polypeptide) and/or at least one T1R3 polypeptide (or a variant, fragment, or chimera of said T1R3 polypeptide), wherein said receptor specifically binds to and/or is activated by sweet taste stimuli.
A cell that expresses a receptor comprised of at least one T1R2 polypeptide (or a variant, fragment, or chimera of said T1R2 polypeptide) and/or at least one T1R3 polypeptide (or a variant, fragment, or chimera of said T1R3 polypeptide), wherein said receptor specifically binds to and/or is activated by sweet taste stimuli.
A cell that stably expresses a receptor comprised of at least one T1R1 polypeptide or a variant, fragment, or chimera of said T1R1 polypeptide and/or at least one T1R3 polypeptide or a variant, fragment, or chimera of said T1R3 polypeptide, wherein said receptor specifically binds to and/or is activated by umami taste stimuli.
A cell that stably expresses a receptor comprised of at least one T1R2 polypeptide or a variant, fragment, or chimera of said T1R2 polypeptide and/or at least one T1R3 polypeptide or a variant, fragment, or chimera of said T1R3 polypeptide, wherein said receptor specifically binds to and/or is activated by sweet taste stimuli.
A method for identifying compounds that modulate taste perception by identifying compounds that bind to, activate, inhibit, and/or modulate a receptor expressed by a cell that stably expresses at least one T1R.
A cell line which inducibly expresses the human T1R1/T1R3 umami taste receptor or the T1R2/T1R3 sweet taste receptor.
A method of inhibiting the T1R1/T1R3 umami taste receptor comprising contacting said receptor with a sweet-taste inhibitor that also inhibits both the T1R1/T1R3 sweet taste receptor and the T1R2/T1R3 taste receptor.
A method for identifying compounds that modulate the T1R1/T1R3 umami taste receptor by screening for compounds that compete with lactisole for binding to and/or inhibiting the T1R1/T1R3 umami taste receptor.
Dependencies are inferred from the claim text.