Senomyx, Inc.

Firmenich Incorporated

Senumyx, Inc.

Hong Xu

Xiaodong Li

Lena Staszewski

Jon Elliot Adler

Fernando Echeverri

Mark Zoller

Sergey Zozulya

Shawn O'Connell

Qing Li

Alexey Pronin

Huixian Tang

Guy Servant

Lena Luukkonen

Lan Zhang

Paul Brust

Yong Yao

Wen Zhao

Donald Karanewsky

Catherine Tachdjian

Vincent Darmohusodo

Andrew P Patron

Chad Priest

Bryan Moyer

Feng Zhang

Thomas P Brady

Victor Selchau

Jon Elliott Adler

Melissa Arellano

Jing Ling

Brett Weylan Ching

Nicholas Callamaras

Femando Echeverri

Hanghui Liu

Keping Wu

Mark Ozeck

Jon Elliot Alder

Hubdan Tang

Hulxian Tang

Donald S Karanewsky

Mark T Zoller

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.

In vitro methods of detecting heteroligomeric T1R2/T2R3-expressing cells that are potentially sensitive to sweet tastants

Newly identified mammalian taste-cell-specific G protein-coupled receptors which function as hetero-oligomeric complexes in the sweet taste transduction pathway, and the genes and cDNA encoding said receptors are described. Specifically, T1R G protein-coupled receptors active in sweet taste signaling as hetero-oligomeric complexes, and the genes and cDNA encoding the same, are described, along with methods for isolating such genes and for isolating and expressing such receptors. Methods for identifying putative taste modulating compounds using such hetero-oligomeric complexes also described, as is a novel surface expression facilitating peptide useful for targeting integral plasma membrane proteins to the surface of a cell.

Methods of using T1R hetero-oligomeric taste receptors to screen for compounds which modulate sweet or umami taste signaling

The present invention relates to the discovery that specific human taste receptors in the T2R taste receptor family respond to particular bitter compounds. Also, the invention relates to the discovery of specific hT2R9 alleles and their disparate activity in functional assays with the same biter ligands. The invention further relates to the use of these T2R receptors in assays for identifying ligands that modulate the activation of these taste receptors by specific bitter ligands and related compounds. These compounds may be used as additives and/or removed from foods, beverages, cosmetics and medicinals in order to modify (block) T2R-associated bitter taste. Also T2R ligands may be used as therapeutics to treat and modulate T2R associated gastrointestinal and metabolic functions as well as treat gastrointestinal and metabolic diseases such as eating disorders, food sensing, fod absorption, obesity, diabetes, Crohn's disease, celiac disease, et al.

Identification of bitter ligands that specifically activate human T2R receptors and related assays for identifying human bitter taste modulators

The invention relates to compounds that specifically bind a T1R1/T1R3 or T1R2/T1R3 receptor or fragments or sub-units thereof. The present invention also relates to the use of hetero-oligomeric and chimeric 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.

T1R hetero-oligomeric taste receptors, cell lines that express said receptors, and taste compounds

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.

Methods of detecting T1R hetero-oligomeric taste receptor expression to identify cells that are potentially sensitive to sweet tastants

Methods of using TIR hetero-oligomeric receptors for screening compounds that modulate sweet or umami taste

The present invention relates to the discovery that specific human taste receptors in the T2R taste receptor family respond to particular bitter compounds. Also, the invention relates to the discovery of specific hT2R9 alleles and their disparate activity in functional assays with the same bitter ligands. The invention further relates to the use of these T2R receptors in assays for identifying ligands that modulate the activation of these taste receptors by specific bitter ligands and related compounds. These compounds may be used as additives and/or removed from foods, beverages, cosmetics and medicinals in order to modify (block) T2R-associated bitter taste. Also T2R ligands may be used as therapeutics to treat and modulate T2R associated gastrointestinal and metabolic functions as well as treat gastrointestinal and metabolic diseases such as eating disorders, food sensing, food absorption, obesity, diabetes, Crohn's disease, celiac disease, et al.

In vitro method using hetero-oligomeric T1R1/T1R3 taste receptors to identify umami tastants

Methods of screening T1R hetero-oligomeric taste receptors for sweet taste modulators

Use of T1R3 venus flytrap region polypeptide to screen for taste modulators

Methods of screening T1R1/T1R3 receptors for compounds that modulate umami taste signaling

The present invention relates to the discovery that specific human taste receptors in the T2R taste receptor family respond to particular bitter compounds. Also, the invention relates to the discovery of specific hT2R9 alleles and their disparate activity in functional assays with the same biter ligands. The invention further relates to the use of these T2R receptors in assays for identifying ligands that modulate the activation of these taste receptors by specific bitter ligands and related compounds. These compounds may be used as additives and/or removed from foods, beverages, cosmetics and medicinals in order to modify (block) T2R-associated bitter taste. Also T2R ligands may be used as therapeutics to treat and modulate T2R associated gastrointestinal and metabolic functions as well as treat gastrointestinal and metabolic diseases such as eating disorders, food sensing, food absorption, obesity, diabetes, Crohn's disease, celiac disease, et al.

Chimeric T1R taste receptor polypeptides and nucleic acid sequences encoding and cell lines that express said chimeric T1R polypeptides

Methods of screening heteromeric T1R2/T1R3 receptors for compounds which modulate sweet taste signaling

Methods of detecting umami tastant-sensitive cells which express heteromeric T1R1/T1R3 receptors

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San Diego, CA, United States of America

Hong Xu