公开(公告)号：US20090221798A1

公开(公告)日：2009-09-03

申请号：US12270857

申请日：2008-11-14

Applicant: Mark Zoller ,  Xiaodong Li ,  Lena Staszewski ,  Shawn O'Connell ,  Sergey Zozulya ,  Jon Elliot Adler ,  Hong Xu ,  Fernando Echeverri

Inventor： Mark Zoller ,  Xiaodong Li ,  Lena Staszewski ,  Shawn O'Connell ,  Sergey Zozulya ,  Jon Elliot Adler ,  Hong Xu ,  Fernando Echeverri

IPC: C07K14/00

CPC classification number: G01N33/5008 ,  A01K2217/05 ,  C07K14/705 ,  G01N33/5041 ,  G01N33/566 ,  G01N2333/726

Abstract: Heteromeric taste receptors are provided. These receptors comprise a first polypeptide which comprises extracellular and transmembrane domains wherein the transmembrane domains are at least 95% identical to the transmembrane domains of specific T1R2 polypeptides, and the extracellular domains are at least 95% identical to the corresponding extracellular domains of the specific T1R2 polypeptide or a different GPCR; and a second polypeptide which comprises extracellular and transmembrane domains wherein the transmembrane domains are at least 95% identical to the transmembrane domains of specific T1R3 polypeptides, and the extracellular domains are at least 95% identical to the corresponding extracellular domains of the specific T1R3 polypeptide or that of a different GPCR.

Abstract translation: 提供异味味觉受体。 这些受体包含第一多肽，其包含细胞外和跨膜结构域，其中跨膜结构域与特异性T1R2多肽的跨膜结构域至少95％相同，并且细胞外结构域与特异性T1R2的相应胞外结构域至少95％相同 多肽或不同的GPCR; 和包含细胞外和跨膜结构域的第二多肽，其中所述跨膜结构域与特异性T1R3多肽的跨膜结构域至少95％相同，并且细胞外结构域与特异性T1R3多肽的相应细胞外结构域至少95％相同，或 不同的GPCR。

公开(公告)号：US20090221001A1

公开(公告)日：2009-09-03

申请号：US12270838

申请日：2008-11-13

Applicant: Mark Zoller ,  Xiaodong Li ,  Lena Staszewski ,  Shawn O'Connell ,  Sergey Zozulya ,  Jon Elliot Adler ,  Hong Xu ,  Fernando Echeverri

Inventor： Mark Zoller ,  Xiaodong Li ,  Lena Staszewski ,  Shawn O'Connell ,  Sergey Zozulya ,  Jon Elliot Adler ,  Hong Xu ,  Fernando Echeverri

IPC: G01N33/566

CPC classification number: G01N33/5008 ,  C12N2503/00 ,  C12N2510/00 ,  C40B30/04 ,  G01N33/6872 ,  G01N2333/726 ,  G01N2500/10

Abstract: Methods for identifying compounds that modulate the T1R1/T1R3 umami taste receptors are provided. These methods comprise screening for compounds that compete with lactisole for binding to and/or inhibiting the T1R1/T1R3 umami taste receptor.

Abstract translation: 提供了鉴定调节T1R1 / T1R3鲜味受体的化合物的方法。 这些方法包括筛选与乳清蛋白竞争结合和/或抑制T1R1 / T1R3鲜味受体的化合物。

公开(公告)号：US20090221000A1

公开(公告)日：2009-09-03

申请号：US12270830

申请日：2008-11-13

Applicant: MARK ZOLLER ,  XIAODONG LI ,  LENA STASZEWSKI ,  SHAWN O'CONNELL ,  SERGEY ZOZULYA ,  JON ELLIOT ADLER ,  HONG XU ,  FERNANDO ECHEVERRI

Inventor： MARK ZOLLER ,  XIAODONG LI ,  LENA STASZEWSKI ,  SHAWN O'CONNELL ,  SERGEY ZOZULYA ,  JON ELLIOT ADLER ,  HONG XU ,  FERNANDO ECHEVERRI

IPC: G01N33/567

CPC classification number: G01N33/5041 ,  A01K2217/05 ,  C07K14/705 ,  C07K2319/00 ,  C12Q1/6876 ,  C12Q2600/124 ,  C12Q2600/158 ,  G01N33/5008 ,  G01N33/566 ,  G01N2333/4719 ,  G01N2333/705 ,  G01N2333/726 ,  G01N2500/04

Abstract: Methods of quantifying the taste of compounds for food and beverages are provided. These methods comprise contacting the compounds with an isolated heteromeric receptor comprising at least one T1R2 polypeptide and at least one T1R3 polypeptide.

Abstract translation: 提供了定量食品和饮料化合物味道的方法。 这些方法包括使化合物与包含至少一种T1R2多肽和至少一种T1R3多肽的分离的异聚受体接触。

公开(公告)号：US20090061458A1

公开(公告)日：2009-03-05

申请号：US12185392

申请日：2008-08-04

Applicant: Jon Elliot Adler ,  Xiaodong Li ,  Lena Staszewski ,  Hong Xu ,  Fernando Echeverri

Inventor： Jon Elliot Adler ,  Xiaodong Li ,  Lena Staszewski ,  Hong Xu ,  Fernando Echeverri

IPC: G01N33/53 ,  G01N33/566

CPC classification number: G01N33/5041 ,  C07K14/723 ,  G01N33/5008 ,  G01N33/5023 ,  G01N33/74 ,  G01N2333/705 ,  G01N2333/726 ,  G01N2500/00

Abstract: 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.

Abstract translation: 描述了在甜味转导途径中作为异寡聚复合物起作用的新鉴定的哺乳动物味细胞特异性G蛋白偶联受体，以及编码所述受体的基因和cDNA。 具体来说，描述了作为异寡聚复合物的甜味信号传导中起作用的T1R G蛋白偶联受体，以及编码相同基因和cDNA的方法，以及用于分离这些基因并分离和表达此类受体的方法。 还描述了使用这种异寡​​聚复合物鉴定推定的味觉调节化合物的方法，以及用于靶向细胞表面的整合质膜蛋白的新颖表达表达促进肽。

公开(公告)号：US20080262087A1

公开(公告)日：2008-10-23

申请号：US11932949

申请日：2007-10-31

Applicant: Mark Zoller ,  Xiaodong Li ,  Lena Staszewski ,  Shawn O'Connell ,  Sergey Zozulya ,  Jon Elliot Adler ,  Hong Xu ,  Fernando Echeverri

Inventor： Mark Zoller ,  Xiaodong Li ,  Lena Staszewski ,  Shawn O'Connell ,  Sergey Zozulya ,  Jon Elliot Adler ,  Hong Xu ,  Fernando Echeverri

IPC: A61K31/192 ,  C07K14/705 ,  C12N5/08 ,  C12N5/06 ,  C07K17/00 ,  A61P27/00 ,  G01N33/566 ,  G01N33/53 ,  C40B30/04 ,  C12Q1/68

CPC classification number: G01N33/5041 ,  A01K2217/05 ,  C07K14/705 ,  C07K2319/00 ,  C12Q1/6876 ,  C12Q2600/124 ,  C12Q2600/158 ,  G01N33/5008 ,  G01N33/566 ,  G01N2333/4719 ,  G01N2333/705 ,  G01N2333/726 ,  G01N2500/04

Abstract: 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.

公开(公告)号：US20080244761A1

公开(公告)日：2008-10-02

申请号：US11932989

申请日：2007-10-31

Applicant: Mark Zoller ,  Xiaodong Li ,  Lena Staszewski ,  Shawn O'Connell ,  Sergey Zozulya ,  Jon Elliot Adler ,  Hong Xu ,  Fernando Echeverri

Inventor： Mark Zoller ,  Xiaodong Li ,  Lena Staszewski ,  Shawn O'Connell ,  Sergey Zozulya ,  Jon Elliot Adler ,  Hong Xu ,  Fernando Echeverri

IPC: A01K67/027 ,  C07K14/00 ,  G01N33/566 ,  C40B30/04 ,  G01N33/569

CPC classification number: G01N33/5008 ,  C12N2503/00 ,  C12N2510/00 ,  C40B30/04 ,  G01N33/6872 ,  G01N2333/726 ,  G01N2500/10

Abstract: 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.

公开(公告)号：US07297543B2

公开(公告)日：2007-11-20

申请号：US10725103

申请日：2003-12-02

Applicant: Mark Zoller ,  Xiaodong Li ,  Lena Staszewski ,  Shawn O'Connell ,  Sergey Zozulya ,  Jon Elliot Adler ,  Hong Xu ,  Fernando Echeverri

Inventor： Mark Zoller ,  Xiaodong Li ,  Lena Staszewski ,  Shawn O'Connell ,  Sergey Zozulya ,  Jon Elliot Adler ,  Hong Xu ,  Fernando Echeverri

IPC: C12N15/74 ,  C12N5/00 ,  C12N5/02 ,  C07K1/00 ,  C07K14/00

CPC classification number: G01N33/5041 ,  A01K2217/05 ,  C07K14/705 ,  C07K2319/00 ,  C12Q1/6876 ,  C12Q2600/124 ,  C12Q2600/158 ,  G01N33/5008 ,  G01N33/566 ,  G01N2333/4719 ,  G01N2333/705 ,  G01N2333/726 ,  G01N2500/04

Abstract: Cells are engineered to stably or transiently express T1R2 and T1R3 polypeptides, desirably in association with a G protein. The resultant heteromeric taste receptor is a sweet taste receptor and responds to sweet taste stimuli such as artificial and natural sweeteners, e.g., saccharin. The invention provides a preferred mammalian cell lines, e.g., HEK-293 cells that stably express T1R2/T1R3 and Gα15 under inducible conditions. These cells are useful in cell-based assays for identifying compounds that elicit or modulate sweet taste.

Abstract translation: 工程改造细胞以稳定或瞬时表达T1R2和T1R3多肽，理想地与G蛋白结合。 所得的异味味觉受体是甜味受体并对甜味刺激如人造天然甜味剂例如糖精作出反应。 本发明提供优选的哺乳动物细胞系，例如在可诱导条件下稳定表达T1R2 / T1R3和Gα15α的HEK-293细胞。 这些细胞可用于鉴定引发或调节甜味的化合物的基于细胞的测定。

公开(公告)号：US20060223117A1

公开(公告)日：2006-10-05

申请号：US11345403

申请日：2006-02-02

Applicant: Bryan Moyer ,  Fernando Echeverri ,  Min Lu ,  Bianca Laita

Inventor： Bryan Moyer ,  Fernando Echeverri ,  Min Lu ,  Bianca Laita

IPC: G01N33/53 ,  C07H21/04 ,  C07K14/705 ,  C07K16/28 ,  C12P21/06

CPC classification number: C07K14/705 ,  G01N33/5041 ,  G01N33/6872

Abstract: Nucleic acid sequences encoding novel splice variants that encode subunits of an ENaC expressed in human taste tissue are provided. These splice variants when expressed in association with other ENaC subunits, i.e., α, β and γ subunits or α, β and Δ subunits may be used to produce amiloride-insensitive ENACs. The resultant amiloride-insensitive ENaCs are useful in in vitro assays for identifying ENaC modulators that modulate taste (enhance or inhibit), particularly human salty taste.

Abstract translation: 提供编码编码人类组织中表达的ENaC亚基的新剪接变体的核酸序列。 当与其它ENaC亚单位，即α，β和γ亚基或α，β和ΔA亚基相关联表达时，这些剪接变体可用于产生不依赖于阿米洛利的ENAC。 所产生的阿米洛利不敏感的ENaC可用于鉴定调节味道（增强或抑制），特别是人类咸味的ENaC调节剂的体外测定。

公开(公告)号：US20060160176A1

公开(公告)日：2006-07-20

申请号：US10725488

申请日：2003-12-03

Applicant: Mark Zoller ,  Xiaodong Li ,  Lena Staszewski ,  Shawn O'Connell ,  Sergey Zozulya ,  Jon Adler ,  Hong Xu ,  Fernando Echeverri

Inventor： Mark Zoller ,  Xiaodong Li ,  Lena Staszewski ,  Shawn O'Connell ,  Sergey Zozulya ,  Jon Adler ,  Hong Xu ,  Fernando Echeverri

IPC: A61K38/17 ,  C07H21/04 ,  C12P21/06 ,  C07K14/705

CPC classification number: G01N33/5041 ,  A01K2217/05 ,  C07K14/705 ,  C07K2319/00 ,  C12Q1/6876 ,  C12Q2600/124 ,  C12Q2600/158 ,  G01N33/5008 ,  G01N33/566 ,  G01N2333/4719 ,  G01N2333/705 ,  G01N2333/726 ,  G01N2500/04

Abstract: Functional assays for identifying compounds that activate or modulate the activation of the T1R1/T1R3 (umami) taste receptor are provided. These assays detect the effect of one or more compounds on the activation of T1R1/T1R3 (umami) taste receptor or on the activation of T1R1/T1R3 umami taste receptor by another compound e.g., monosodium glutamate, lactisole, or another unami taste modulator. These assays preferably are cell-based functional assays and typically use cells, e.g., HEK-293 cells that express a G protein such as Gα15, Gα16 or gustducin. Compounds identified in the disclosed functional assays are potentially useful as flavor additives in compositions for human or animal consumption.

Abstract translation: 提供用于鉴定激活或调节T1R1 / T1R3（鲜味）味觉受体的活化的化合物的功能测定。 这些测定法检测一种或多种化合物对T1R1 / T1R3（鲜味）味觉受体活化的影响，或通过另一种化合物如谷氨酸钠，乳清酸或另一种非口味调节剂对T1R1 / T1R3鲜味受体的活化。 这些测定优选是基于细胞的功能测定，并且通常使用细胞，例如表达G蛋白例如Gα，αα16或Gustducin的HEK-293细胞。 在公开的功能测定中鉴定的化合物在用于人类或动物消费的组合物中可用作风味添加剂。

公开(公告)号：US06955887B2

公开(公告)日：2005-10-18

申请号：US09897427

申请日：2001-07-03

Applicant: Jon Elliot Adler ,  Xiaodong Li ,  Lena Staszewski ,  Hong Xu ,  Fernando Echeverri

Inventor： Jon Elliot Adler ,  Xiaodong Li ,  Lena Staszewski ,  Hong Xu ,  Fernando Echeverri

IPC: C07K14/705 ,  G01N33/566 ,  G01N33/53 ,  C07K1/00 ,  C07K14/00 ,  C07K16/00 ,  G01N33/567

CPC classification number: C07K14/705 ,  C07K2319/00 ,  G01N33/566 ,  G01N2333/726 ,  G01N2500/04

Abstract: 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.

Abstract translation: 描述了在甜味转导途径中作为异寡聚复合物起作用的新鉴定的哺乳动物味细胞特异性G蛋白偶联受体，以及编码所述受体的基因和cDNA。 具体来说，描述了作为异寡聚复合物的甜味信号传导中起作用的T1R G蛋白偶联受体，以及编码相同基因和cDNA的方法，以及用于分离这些基因并分离和表达此类受体的方法。 还描述了使用这种异寡​​聚复合物鉴定推定的味觉调节化合物的方法，以及用于靶向细胞表面的整合质膜蛋白的新颖表达表达促进肽。