公开(公告)号：US07294474B2

公开(公告)日：2007-11-13

申请号：US10725475

申请日：2003-12-03

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

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

IPC分类号： G01N33/53 ,  G01N33/567 ,  C07K1/00 ,  C07K14/00 ,  C07K17/00

CPC分类号： 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

摘要： Functional assays for identifying compounds that activate or modulate the activation of the T1R2/T1R3 (sweet) taste receptor are provided. These assays detect the effect of one or more compounds on the activation of T1R2/T1R3 (sweet) taste receptor or on the activation of T1R2/T1R3 sweet taste receptor by another, compound e.g., saccharin or another artificial or natural sweetener. These assays preferably are cell-based functional assays and typically use cells, e.g., HEK-293 cells that stably express a G protein such as Gα15, Gα16 or gustducin. Compounds identified in the disclosed functional assays are potentially useful as additives in compositions for human or animal consumption.

摘要翻译： 提供用于鉴定激活或调节T1R2 / T1R3（甜味）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T1R2 / T1R3（甜味）感受器的激活或另一种化合物例如糖精或另一种人造或天然甜味剂对T1R2 / T1R3甜味受体的活化的影响。 这些测定优选是基于细胞的功能测定，并且通常使用细胞，例如稳定表达G蛋白如GαA，αα16或gustducin的HEK-293细胞。 在所公开的功能测定中鉴定的化合物潜在地用作用于人或动物消费的组合物中的添加剂。

公开(公告)号：US08802377B2

公开(公告)日：2014-08-12

申请号：US13615778

申请日：2012-09-14

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

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

IPC分类号： G01N33/53 ,  G01N33/567 ,  C12Q1/68

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

摘要： 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.

摘要翻译： 本发明涉及T1R受体组装形成功能性味觉受体的发现。 特别地，已经发现，T1R1和T1R3的共表达导致对鲜味刺激（包括谷氨酸钠）起反应的味觉感受器。 此外，已经发现，T1R2和T1R3受体的共表达导致对包括天然存在的和人造甜味剂的甜味刺激有反应的味觉受体。 本发明还涉及在测定中使用包含T1R1 / T1R3和T1R2 / T1R3的异低聚味觉感受器来鉴定分别响应于鲜味刺激和甜味刺激的化合物。

公开(公告)号：US08119402B2

公开(公告)日：2012-02-21

申请号：US12270848

申请日：2008-11-13

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

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

IPC分类号： C12N5/00 ,  C12N5/02 ,  A61K49/00 ,  A01N61/00

CPC分类号： 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

摘要： Methods of inhibiting umami taste receptors are provided. These methods comprise contacting T1R1/T1R3 umami taste receptors with a sweet-taste inhibitor that also inhibits both the T1R1/T1R3 umami taste receptor and the T1R2/T1R3 sweet taste receptor.

摘要翻译： 提供了抑制鲜味受体的方法。 这些方法包括使T1R1 / T1R3鲜味受体与也抑制T1R1 / T1R3鲜味受体和T1R2 / T1R3甜味受体的甜味抑制剂接触。

公开(公告)号：US20110201028A1

公开(公告)日：2011-08-18

申请号：US13023502

申请日：2011-02-08

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

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

IPC分类号： G01N33/53 ,  C12N1/00 ,  C12N5/10

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

摘要： 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：US07892765B2

公开(公告)日：2011-02-22

申请号：US12185392

申请日：2008-08-04

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

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

IPC分类号： G01N33/53 ,  G01N33/567

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

摘要： 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.

摘要翻译： 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的表达表达促进肽。

公开(公告)号：US20090221797A1

公开(公告)日：2009-09-03

申请号：US12270834

申请日：2008-11-13

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

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

IPC分类号： C07K19/00

CPC分类号： 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

摘要： 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 T1R1 polypeptides, and the extracellular domains are at least 95% identical to the corresponding extracellular domains of the specific T1R1 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.

摘要翻译： 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T1R1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T1R1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：US20090221796A1

公开(公告)日：2009-09-03

申请号：US12270813

申请日：2008-11-13

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

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

IPC分类号： C07K14/00

CPC分类号： 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

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

摘要翻译： 提供异味味觉受体。 这些受体包含含有细胞外结构域和跨膜结构域的第一多肽，其中细胞外结构域与特异性T1R2多肽的细胞外结构域至少95％相同，并且跨膜结构域与特异性T1R2多肽的相应跨膜结构域至少95％相同 或不同的GPCR; 和包含细胞外和跨膜结构域的第二多肽，其中细胞外结构域与特异性T1R3多肽的细胞外结构域至少95％相同，并且跨膜结构域与特异性T1R3多肽的相应跨膜结构域至少95％相同或不同 GPCR。

公开(公告)号：US20090221709A1

公开(公告)日：2009-09-03

申请号：US12270846

申请日：2008-11-13

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

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

IPC分类号： A61K31/19

CPC分类号： 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

摘要： Methods of modifying taste sensation in an animal are provided. These methods comprise administrating compounds that modulate T1R1/T1R3 or T1R2/T1R3 receptors.

摘要翻译： 提供了改善动物味觉的方法。 这些方法包括施用调节T1R1 / T1R3或T1R2 / T1R3受体的化合物。

公开(公告)号：US20080248996A1

公开(公告)日：2008-10-09

申请号：US11932493

申请日：2007-10-31

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

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

IPC分类号： A61K38/00 ,  C07K14/00 ,  C12N5/06 ,  G01N33/566 ,  G01N33/569 ,  A61P27/00 ,  A01K67/027 ,  G01N33/53 ,  C40B30/04 ,  A61K47/00

CPC分类号： 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

摘要： 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：US07419791B2

公开(公告)日：2008-09-02

申请号：US11050804

申请日：2005-02-07

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

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

IPC分类号： G01N33/53 ,  G01N33/567 ,  C12P21/06 ,  C12N1/20 ,  C12N15/74

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

摘要： 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.

摘要翻译： 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的表达表达促进肽。