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    Olfactory cyclic nucleotide-gated channel cell-based assays to identify T1R and T2R taste modulators
    6.
    发明申请
    Olfactory cyclic nucleotide-gated channel cell-based assays to identify T1R and T2R taste modulators 审中-公开
    基于嗅觉环状核苷酸门控通道细胞的测定来鉴定T1R和T2R调味剂

    公开(公告)号：US20060134693A1

    公开(公告)日：2006-06-22

    申请号：US11006802

    申请日：2004-12-08

    申请人： Guy Servant ,  Mark Ozeck ,  Paul Brust ,  Hong Xu ,  Lena Staszewski ,  Jon Adler ,  Mark Zoller ,  Nicholas Callamaras ,  Alexey Pronin ,  Bryan Moyer

    发明人： Guy Servant ,  Mark Ozeck ,  Paul Brust ,  Hong Xu ,  Lena Staszewski ,  Jon Adler ,  Mark Zoller ,  Nicholas Callamaras ,  Alexey Pronin ,  Bryan Moyer

    IPC分类号： G01N33/53 ,  C07K14/705

    CPC分类号： C07K14/705 ,  G01N33/5008 ,  G01N33/502 ,  G01N33/566 ,  G01N2333/726

    摘要： Screening assays, preferably high throughput, are provided that screen libraries of candidate compounds to identify agonists, antagonists, enhancers or modulators of taste receptors (bitter, sweet or savory (umami) taste receptor) using test cells that co-express at least one functional taste receptor and an olfactory cyclic nucleotide-gated channel (oCNGC). (The oCNGC preferably comprises at least one mutation in one or more subunits that renders the resultant oCNGC more sensitive to CAMP (which in turn enhances the sensitivity of assay using this oCNGC). These taste modulatory compounds are identified based on their effect on oCNGC activity, e.g., using fluorimetric assays that screen for changes in intracellular calcium or sodium concentration in test cells that co-express at least one taste receptor, oCNGC and a Gαi/o protein.

    摘要翻译： 提供筛选分析，优选高通量，使用候选化合物的筛选文库，以鉴定共感染至少一种功能性的测试细胞的味觉受体（苦味，甜味或咸味（鲜味）味觉受体）的激动剂，拮抗剂，增强剂或调节剂 味觉受体和嗅觉环状核苷酸门控通道（oCNGC）。 （oCNGC优选地包含一个或多个亚基中的至少一个突变，使得所得到的oCNGC对CAMP更敏感（反过来又增强了使用该oCNGC的测定的灵敏度）。这些口味调节化合物基于它们对oCNGC活性的影响 例如，使用荧光测定法筛选测试细胞中细胞内钙或钠浓度的变化，所述测试细胞共表达至少一种味觉受体（oCNGC）和蛋白质（G）。

    Identification of bitter ligands that specifically activate human T2R receptors and related assays for identifying human bitter taste modulators
    9.
    发明授权
    Identification of bitter ligands that specifically activate human T2R receptors and related assays for identifying human bitter taste modulators 有权
    识别特异性激活人T2R受体的苦配体和相关测定法，用于鉴定人类苦味调节剂

    公开(公告)号：US08715946B2

    公开(公告)日：2014-05-06

    申请号：US13019580

    申请日：2011-02-02

    申请人： Xiaodong Li ,  Hong Xu ,  Qing Li ,  Huixian Tang ,  Alexey Pronin

    发明人： Xiaodong Li ,  Hong Xu ,  Qing Li ,  Huixian Tang ,  Alexey Pronin

    IPC分类号： G01N33/567 ,  C07K14/705

    CPC分类号： G01N33/566 ,  G01N33/5008 ,  G01N33/5023 ,  G01N2500/00 ,  G01N2500/10

    摘要： 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 bitter 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.

    摘要翻译： 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，本发明涉及特异性hT2R9等位基因的发现及其在具有相同苦味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。