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    Methods of screening heteromeric T1R2/T1R3 receptors which modulate sweet taste signaling
    3.
    发明授权
    Methods of screening heteromeric T1R2/T1R3 receptors which modulate sweet taste signaling 有权
    筛选调节甜味信号的异源性T1R2 / T1R3受体的方法

    公开(公告)号：US08323912B2

    公开(公告)日：2012-12-04

    申请号：US13023502

    申请日：2011-02-08

    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 ,  C07K1/00 ,  C07K14/00 ,  C07K17/00

    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.

    Abstract translation: 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。 此外，本发明涉及稳定或瞬时共表达T1R1和T1R3的组合的细胞系的组成; 或T1R2和T1R3; 在组成型或诱导性条件下。 还提供了在基于细胞的测定中使用这些细胞系以鉴定鲜味和甜味调节化合物，特别是通过使用荧光成像检测受体活性的高通量筛选测定。 最后，本发明涉及一些发现，一些化合物，例如乳酸，抑制人T1R2 / T1R3和T1R1 / T1R3受体的活性，因此抑制甜味和鲜味，这表明这些受体可能是唯一的甜味和鲜味 受体。

    T1R TASTE RECEPTORS AND GENES ENCODING SAME
    5.
    发明申请
    T1R TASTE RECEPTORS AND GENES ENCODING SAME 有权
    T1R TASTE受体和编码它们的基因

    公开(公告)号：US20120164664A1

    公开(公告)日：2012-06-28

    申请号：US13288322

    申请日：2011-11-03

    Applicant: Jon Elliot Adler ,  Xiaodong Li ,  Lena Staszewski ,  Shawn O'Connell ,  Sergey Zozulya

    Inventor： Jon Elliot Adler ,  Xiaodong Li ,  Lena Staszewski ,  Shawn O'Connell ,  Sergey Zozulya

    IPC: G01N33/566 ,  C07K14/705 ,  C12N1/19 ,  C12N5/10 ,  C12N1/21 ,  C12N15/12 ,  C12N15/63

    CPC classification number: C07K14/723 ,  C07K14/705 ,  C07K2319/00 ,  C12Q1/6883 ,  G01N33/5041 ,  G01N33/6872 ,  G01N33/74 ,  G01N2333/726 ,  G06F19/12

    Abstract: 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.

    Abstract translation: 描述了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。 具体地说，描述了活跃于味觉信号传导中的T1R G蛋白偶联受体以及编码相同基因的cDNA，以及用于分离这些基因并用于分离和表达此类受体的方法。 还描述了用于表示哺乳动物中特定味觉刺激的味觉感知的方法，以及用于产生哺乳动物中引发预定味觉的新颖分子或分子组合的方法，以及用于模拟一种或多种口味的方法。 此外，还公开了哺乳动物刺激或阻止味觉的方法。

    Human T1R2 nucleic acid sequences and polypeptides
    7.
    发明授权
    Human T1R2 nucleic acid sequences and polypeptides 有权
    人T1R2核酸序列和多肽

    公开(公告)号：US08138322B2

    公开(公告)日：2012-03-20

    申请号：US12177925

    申请日：2008-07-23

    Applicant: Jon Elliot Adler ,  Xiaodong Li ,  Lena Staszewski ,  Shawn O'Connell ,  Sergey Zozulya

    Inventor： Jon Elliot Adler ,  Xiaodong Li ,  Lena Staszewski ,  Shawn O'Connell ,  Sergey Zozulya

    IPC: C12N15/12 ,  C12N15/62 ,  C07K14/705

    CPC classification number: C07K14/723 ,  C07K14/705 ,  C07K2319/00 ,  C12Q1/6883 ,  G01N33/5041 ,  G01N33/6872 ,  G01N33/74 ,  G01N2333/726 ,  G06F19/12

    Abstract: Binding assays for identifying compounds that modulate human T1R2 polypeptide associated taste are disclosed. These assays detect the specific binding of compounds to a human T1R2 polypeptide or the modulation of the specific binding of a compound that specifically binds to a human T1R2 polypeptide. The binding assays may include the use of detectable labels, e.g., radionuclides, enzymes, fluorophases, and the like. Compounds identified in these binding assays have putative application as T1R2 taste modulators, particularly sweet taste, and potentially are useful additives in compositions for human or animal consumption.

    Abstract translation: 公开了用于鉴定调节人类T1R2多肽相关味道的化合物的结合测定法。 这些测定法检测化合物与人T1R2多肽的特异性结合，或调节与人T1R2多肽特异性结合的化合物的特异性结合。 结合测定可以包括使用可检测的标记，例如放射性核素，酶，氟化酶等。 在这些结合测定中鉴定的化合物具有T1R2味道调节剂，特别是甜味的推定应用，并且潜在地是用于人或动物消费的组合物中有用的添加剂。

    T1R HETERO-OLIGOMERIC TASTE RECEPTORS AND CELL LINES THAT EXPRESS SAID RECEPTORS AND USE THEREOF FOR IDENTIFICATION OF TASTE COMPOUNDS
    10.
    发明申请
    T1R HETERO-OLIGOMERIC TASTE RECEPTORS AND CELL LINES THAT EXPRESS SAID RECEPTORS AND USE THEREOF FOR IDENTIFICATION OF TASTE COMPOUNDS 有权
    T1R异源低聚物受体和细胞系，其表达所接受的受体及其用于鉴定化合物的用途

    公开(公告)号：US20110201020A1

    公开(公告)日：2011-08-18

    申请号：US13023462

    申请日：2011-02-08

    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: G01N33/53 ,  C07K14/705 ,  C12N5/071

    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.

    Abstract translation: 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。 此外，本发明涉及稳定或瞬时共表达T1R1和T1R3的组合的细胞系的组成; 或T1R2和T1R3; 在组成型或诱导性条件下。 还提供了在基于细胞的测定中使用这些细胞系以鉴定鲜味和甜味调节化合物，特别是通过使用荧光成像检测受体活性的高通量筛选测定。 最后，本发明涉及一些发现，一些化合物，例如乳酸，抑制人T1R2 / T1R3和T1R1 / T1R3受体的活性，因此抑制甜味和鲜味，这表明这些受体可能是唯一的甜味和鲜味 受体。

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