Senomyx, Inc.

University of California

The Government of the United States of America As Represented by the Secretary of the Deptartment of Health and Human Services

Firmenich Incorporated

Other

Senumyx, Inc.

Jon Elliot Adler

Shawn O'Connell

Lena Staszewski

Sergey Zozulya

Xiaodong Li

Hong Xu

Fernando Echeverri

Mark Zoller

Charles S Zuker

Ken Mueller

Xiadong Li

Nick Ryba

Mark A Hoon

Lena Luukkonen

Juergen Lindemeier

Alexey Pronin

Guy Servant

Huixian Tang

Paul Brust

Walter Keung

Judy Connor

Bryan Moyer

Nicholas Callamaras

Femando Echeverri

Shawn O'connell

Nicholas Jp Ryba

David M Cowan

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, and the genes and cDNA encoding said receptors are described. Specifically, T1R G protein-coupled receptors active in taste signaling, 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 representing taste perception of a particular taste stimulus in a mammal are also described, as are methods for generating novel molecules or combinations of molecules that elicit a predetermined taste perception in a mammal, and methods for simulating one or more tastes. Further, methods for stimulating or blocking taste perception in a mammal are also disclosed.

T1R taste receptors and genes encoding same

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 invention relates to the identification of taste receptors and cells which express these taste receptors which are involved in sweet and umami taste transduction. Also, the invention relates to the use of these taste receptors and cells which express these taste receptors in assays for the identification of taste modulatory compounds.

TIR taste receptors and genes encoding same

Newly identified mammalian taste-cell-specific G Protein-Coupled Receptors and the genes encoding said receptors are described. Specifically, T2R taste G Protein-Coupled Receptors that are believed to be involved in bitter taste sensation, and the genes encoding the same, are described, along with methods for isolating such genes and for isolating and expressing such receptors. Methods for representing taste perception of a particular tastant in a mammal are also described, as are methods for generating a novel molecules or combinations of molecules that elicit a predetermined taste perception in a mammal, and methods for simulating one or more tastes.

T2R taste receptors and genes encoding same

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 are provided for identifying human and non-human primate cells which respond to sweet tastants. These methods screen for human or non-human primate cells which express a polypeptide which binds to or responds to sweet tastants. These cells may be used in binding and functional assays to screen for compounds which modulate sweet taste.

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

The invention provides isolated nucleic acid and amino acid sequences of sensory cell specific G-protein coupled receptors, antibodies to such receptors, methods of detecting such nucleic acids and receptors, and methods of screening for modulators of sensory cell specific G-protein coupled receptors.

G-protein coupled receptor polypeptides involved in sensory transduction

The invention provides nucleic acid and amino acid sequences for a novel family of taste transduction G-protein coupled receptors, antibodies to such receptors, methods of detecting such nucleic acids and receptors, and methods of screening for modulators of taste transduction G-protein coupled receptors.

Method for identifying compounds that modulate a T2R taste receptor

Newly identified mammalian taste-cell-specific G protein-coupled receptors, and the genes and cDNA encoding said receptors are provided. Specifically, T1R G protein-coupled receptors active in taste signaling, and the genes and cDNA encoding the same, are provided, along with methods for isolating such genes and for isolating and expressing such receptors.

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

Growing community of inventors

San Diego, CA, United States of America

Jon Elliot Adler