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：US20090045533A1

公开(公告)日：2009-02-19

申请号：US11960663

申请日：2007-12-19

Applicant: CHE-YUAN HSU ,  CHENG-WEN SU ,  YI-QIANG XU ,  ZHEN-YUAN ZHAI ,  GANG HUANG ,  LEI CHEN ,  HUAN-HONG XU ,  YAN-MIN WANG

Inventor： CHE-YUAN HSU ,  CHENG-WEN SU ,  YI-QIANG XU ,  ZHEN-YUAN ZHAI ,  GANG HUANG ,  LEI CHEN ,  HUAN-HONG XU ,  YAN-MIN WANG

IPC: B29D11/00

CPC classification number: B29C45/162 ,  B29C45/14778 ,  B29C45/1671 ,  B29C45/561 ,  B29K2995/002 ,  B29K2995/0026 ,  B29L2011/0016 ,  B29L2031/3475

Abstract: A mold (20) for making a housing includes a female mold (22) and a rotatable male mold (24). The female mold has a first recessed mold portion (221) and a second recessed mold portion (222) defined therein. The male mold includes a first mold core (242), a second mold core (244), and a movable compression assembly (246). The first mold core has a first stepped portion (2422) and a second stepped portion (2424) protruding from the first stepped portion. The second mold core has a projection wall (2441) protruding from the male mold and a molding groove (2442) defined by the projection wall. The projection wall is matingly engageable into any one of the first recessed mold portion and the second recessed mold portion. The movable compression assembly is received in the molding groove and capable of moving towards to the female mold.

Abstract translation: 用于制造壳体的模具（20）包括阴模（22）和可旋转阳模（24）。 阴模具有限定在其中的第一凹入模具部分（221）和第二凹入模具部分（222）。 阳模包括第一模芯（242），第二模芯（244）和可移动压缩组件（246）。 第一模芯具有从第一台阶部分突出的第一台阶部分（2422）和第二阶梯部分（2424）。 第二模芯具有从阳模突出的突出壁（2441）和由突出壁限定的模制槽（2442）。 突出壁可配合地接合到第一凹入模具部分和第二凹入模具部分中的任何一个中。 可移动压缩组件被容纳在模制槽中并且能够朝向阴模移动。

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：US20080244762A1

公开(公告)日：2008-10-02

申请号：US11939408

申请日：2007-11-13

Applicant: Mark ZOLLER ,  Xiaodong Li ,  Lena Staszewski ,  Shawn O'Connell ,  Sergey Zozulya ,  Jon Elliot Adler ,  Hong Xu ,  Fermando Echeveri

Inventor： Mark ZOLLER ,  Xiaodong Li ,  Lena Staszewski ,  Shawn O'Connell ,  Sergey Zozulya ,  Jon Elliot Adler ,  Hong Xu ,  Fermando Echeveri

IPC: A01K67/027 ,  C07K14/00 ,  G01N33/566 ,  G01N33/53 ,  C40B30/04 ,  C12N5/06 ,  G01N33/569

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

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：US20080038739A1

公开(公告)日：2008-02-14

申请号：US11766974

申请日：2007-06-22

Applicant: Xiaodong LI ,  Hong Xu ,  Qing Li ,  Huixian Tang ,  Alexey Pronin

Inventor： Xiaodong LI ,  Hong Xu ,  Qing Li ,  Huixian Tang ,  Alexey Pronin

IPC: G01N33/53 ,  C12Q1/02 ,  C12Q1/68

CPC classification number: G01N33/566 ,  G01N33/5008 ,  G01N33/5023 ,  G01N2500/00 ,  G01N2500/10

Abstract: 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.

Abstract translation: 本发明涉及T2R味觉受体家族中的特定人味受体对特定苦味化合物的反应的发现。 此外，本发明还涉及特异性hT2R9等位基因的发现及其在具有相同配体配体的功能测定中的不同活性。 本发明还涉及这些T2R受体在用于鉴定通过特定的苦配体和相关化合物调节这些味觉受体的活化的配体的测定中的用途。 这些化合物可以用作添加剂和/或从食品，饮料，化妆品和药物中去除，以便改变（阻断）T2R相关的苦味。 也可以使用T2R配体作为治疗和调节T2R相关胃肠和代谢功能以及治疗胃肠道和代谢疾病如饮食失调，食物感觉，食物吸收，肥胖，糖尿病，克罗恩病，乳糜泻等的治疗剂。

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：US07208290B2

公开(公告)日：2007-04-24

申请号：US10318031

申请日：2002-12-13

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

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

IPC: C12P21/06 ,  C12N1/20 ,  C12N15/74

CPC classification number: C07K14/4722 ,  A01K2217/05

Abstract: The invention provides a series of chimeric Gα15 protein variants that couple to certain GPCRs more efficiently than the native Gα15 protein. These chimeric Gα15 protein variants can be used to discover and analyze modulators of GPCRs (especially those that mediate taste perception).

Abstract translation: 本发明提供了一系列比天然Galpha 15蛋白更有效地耦合到某些GPCR的嵌合Gα15N1蛋白质变体。 可以使用这些嵌合的α155蛋白质变体来发现和分析GPCRs的调节剂（特别是介导味觉的调节剂）。

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：US07022488B2

公开(公告)日：2006-04-04

申请号：US10770127

申请日：2004-02-03

Applicant: Guy Servant ,  Mark Ozeck ,  Paul Brust ,  Hong Xu

Inventor： Guy Servant ,  Mark Ozeck ,  Paul Brust ,  Hong Xu

IPC: G01N33/53 ,  G01N33/567 ,  C12P21/06 ,  C12N1/20

CPC classification number: G01N33/5041 ,  G01N33/5008 ,  G01N33/566 ,  G01N2333/726 ,  G01N2500/10

Abstract: The invention resides in part in the discovery that G proteins other than Gα15 couples to T1R and T2R taste receptors, particularly Gi proteins such as Gαi. Related to this discovery, the invention provides cell-based assay methods for identifying compounds that modulate the activity of specific T1R or T2R taste receptors or which modulate the effect of other T1R or T2R modulators on T1R or T2R activity. These assay methods preferably detect the effect of a putative T1R or T2R modulator compound on MAPK activation, cAMP accumulation, or adenylyl cyclase activity or another signaling pathway regulated by Gi proteins. The level of MAPK activation, cAMP accumulation or adenylyl cyclase is preferably determined by immunoassay methods that use ligands (monoclonal or polyclonal antibodies) that specifically bind an activated (phosphorylated) MAPK, cAMP, or adenylyl cyclase.

Abstract translation: 本发明部分地在于以下发现：除了Galpha 15之外的G蛋白与T1R和T2R味觉受体，特别是GII蛋白（例如Gα- SUB>。 与该发现有关，本发明提供用于鉴定调节特异性T1R或T2R味觉受体的活性的化合物的基于细胞的测定方法，或调节其它T1R或T2R调节剂对T1R或T2R活性的影响。 这些测定方法优选地检测推定的T1R或T2R调节剂化合物对MAPK激活，cAMP积聚或腺苷酸环化酶活性或由GII蛋白调节的另一信号传导途径的影响。 MAPK活化水平，cAMP积聚或腺苷酸环化酶优选通过使用特异性结合活化（磷酸化）MAPK，cAMP或腺苷酸环化酶的配体（单克隆或多克隆抗体）的免疫测定方法来确定。