Senomyx, Inc.

Firmenich Incorporated

Senumyx, Inc.

Fernando Echeverri

Xiaodong Li

Hong Xu

Jon Elliot Adler

Lena Staszewski

Sergey Zozulya

Shawn O'Connell

Mark Zoller

Lena Luukkonen

Bryan Moyer

Min Lu

Hong Chang

Jon Elliott Adler

Yi Han

Jon Elliot Alder

Kun Wang

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 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

This invention relates to electrophysiological assays that measure sodium conductance activity of a delta human epithelial sodium channel (ENaC) in the presence and absence of delta hENaC enhancers. Also, the invention generally relates to assays for identifying compounds that enhance the activity of delta hENaC, especially in an oocyte expression system. These compounds have potential application in modulating (enhancing) salty taste perception.

Assays and enhancers of the human delta ENaC sodium channel

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

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

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

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. 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.

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

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

Cell lines expressing T1R2/T1R3 hetero-oligomeric taste receptors and assay system thereof for identification of taste compounds

In vitro methods of detecting cells sensitive to sweet tastants by detecting expression of hetero-oligomeric T1R2/T1R3 taste receptors

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Chula Vista, CA, United States of America

Fernando Echeverri