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    Methods for identifying inhibitors of chlorophyll synthase
    3.
    发明申请
    Methods for identifying inhibitors of chlorophyll synthase 审中-公开
    鉴定叶绿素合酶抑制剂的方法

    公开(公告)号：US20050130118A1

    公开(公告)日：2005-06-16

    申请号：US10737014

    申请日：2003-12-16

    申请人： Abubakr Aslamkhan ,  Lining Guo ,  Rao Mulpuri ,  Neil Hoffman ,  Susanne Kjemtrup ,  Jocelyn Kearney ,  Cory Christensen ,  Keith Davis ,  Adel Zayed ,  Robert Ascenzi ,  Douglas Boyes

    发明人： Abubakr Aslamkhan ,  Lining Guo ,  Rao Mulpuri ,  Neil Hoffman ,  Susanne Kjemtrup ,  Jocelyn Kearney ,  Cory Christensen ,  Keith Davis ,  Adel Zayed ,  Robert Ascenzi ,  Douglas Boyes

    IPC分类号： C12Q1/00 ,  G01N33/573

    CPC分类号： G01N33/573

    摘要： The present inventors have discovered that antisense suppression of a chlorophyll synthase (CS) gene results in plants exhibiting one or more of chlorosis, reduced growth, and altered development. Thus, the present inventors have discovered that the protein encoded by the CS gene is essential for normal plant growth and development, and is useful as a target for the identification of compounds as antibiotics and herbicides, especially herbicides. The present invention is directed to methods for identifying inhibitors of a CS enzyme by incubating a CS polypeptide with a chlorophyllide and a phopholipid substrate in the presence and absence of a test compound under conditions suitable for the CS enzyme activity, adding a solution to the incubation reactions comprising a water immiscible organic solvent, a water-soluble alcohol, and a water-soluble dye that absorbs in the range of one or both the excitation and emission wavelength ranges of the chlorophyllide substrate, and measuring the fluorescence of the incubation reactions at from about 650 to 750 nm, using from about 425 to 445 nm as excitation wavelength, wherein a decrease in the fluorescence in the presence of the test compound indicates that the compound is a CS inhibitor.

    摘要翻译： 本发明人已经发现，叶绿素合酶（CS）基因的反义抑制导致植物表现出一种或多种褪绿，生长减少和改变发育。 因此，本发明人已经发现，由CS基因编码的蛋白质对于正常的植物生长和发育是必需的，并且可用作鉴定作为抗生素和除草剂，特别是除草剂的化合物的靶标。 本发明涉及通过在适合于CS酶活性的条件下，在存在和不存在测试化合物的情况下，将CS多肽与叶绿素和磷脂底物一起温育来鉴定CS酶抑制剂的方法，向培养基中加入溶液 包括与水不溶混的有机溶剂，水溶性醇和在所述叶绿素底物的激发和发射波长范围中的一个或两个的范围内吸收的水溶性染料的反应，以及测量从 约650至750nm，使用约425至445nm作为激发波长，其中在测试化合物存在下荧光的降低表明该化合物是CS抑制剂。

    Determining liver toxicity of an agent using metabolite biomarkers
    6.
    发明授权
    Determining liver toxicity of an agent using metabolite biomarkers 有权
    使用代谢物生物标志物测定药物的肝脏毒性

    公开(公告)号：US08658351B2

    公开(公告)日：2014-02-25

    申请号：US13148082

    申请日：2010-02-05

    申请人： Michael Milburn ,  Lining Guo ,  Jacob Edward Wulff ,  Kay A. Lawton

    发明人： Michael Milburn ,  Lining Guo ,  Jacob Edward Wulff ,  Kay A. Lawton

    IPC分类号： C12Q1/00

    CPC分类号： G01N33/5014 ,  G01N33/5067 ,  G01N33/5088

    摘要： The present invention provides various biomarkers for hepatotoxicity and various methods of using the biomarkers Some of the biomarkers within the scope of this invention are cholate, glycochenodeoxycholate, glycocholate, taurine, 3-hyroxy-2-ethylpropionate, 4-imidazoleacetate, tyramine, anthranilate, 2′-deoxycytidine, N-acetyl aspartate (NAA), beta-hydroxy-hexanoate, and sarcosine (N-methylglycine) The methods of using the biomarkers include exposing a first hepatocyte culture to a test agent and comparing the levels of the one or more biomarkers obtained in the first hepatocyte culture to the levels of the one or more biomarkers obtained in a second hepatocyte culture without the test agent, where differential levels of the one or more biomarkers in the first hepatocyte culture as compared to the levels in the second hepatocyte culture is indicative of the test agent being a hepatotoxicant.

    摘要翻译： 本发明提供用于肝毒性的各种生物标志物和使用生物标志物的各种方法本发明范围内的一些生物标志物是胆酸，甘油脱氧胆酸，甘氨胆酸，牛磺酸，3-羟基-2-乙基丙酸酯，4-咪唑乙酸酯，酪胺，邻氨基苯甲酸酯， 2'-脱氧胞苷，N-乙酰天冬氨酸（NAA），β-羟基己酸酯和肌氨酸（N-甲基甘氨酸）使用生物标志物的方法包括将第一肝细胞培养物暴露于测试试剂，并比较其中一种或多种 在第一肝细胞培养物中获得的更多生物标志物在没有测试剂的第二肝细胞培养物中获得的一种或多种生物标志物的水平，其中第一肝细胞培养物中的一种或多种生物标志物的差异水平与第二次肝细胞培养物中的水平相比 肝细胞培养表明试验剂是肝毒性剂。

    Determination of the Liver Toxicity of an Agent
    7.
    发明申请
    Determination of the Liver Toxicity of an Agent 有权
    药物肝脏毒性的测定

    公开(公告)号：US20110300571A1

    公开(公告)日：2011-12-08

    申请号：US13148082

    申请日：2010-02-05

    申请人： Michael Milburn ,  Lining Guo ,  Jacob Edward Wulff ,  Kay A. Lawton

    发明人： Michael Milburn ,  Lining Guo ,  Jacob Edward Wulff ,  Kay A. Lawton

    IPC分类号： C12Q1/02 ,  G01N27/00

    CPC分类号： G01N33/5014 ,  G01N33/5067 ,  G01N33/5088

    摘要： The present invention provides various biomarkers for hepatotoxicity and various methods of using the biomarkers Some of the biomarkers within the scope of this invention are cholate, glycochenodeoxycholate, glycocholate, taurine, 3-hyroxy-2-ethylpropionate, 4-imidazoleacetate, tyramine, anthranilate, 2′-deoxycytidine, N-acetyl aspartate (NAA), beta-hydroxy-hexanoate, and sarcosine (N-methylglycine) The methods of using the biomarkers include exposing a first hepatocyte culture to a test agent and comparing the levels of the one or more biomarkers obtained in the first hepatocyte culture to the levels of the one or more biomarkers obtained in a second hepatocyte culture without the test agent, where differential levels of the one or more biomarkers in the first hepatocyte culture as compared to the levels in the second hepatocyte culture is indicative of the test agent being a hepatotoxicant.

    摘要翻译： 本发明提供用于肝毒性的各种生物标志物和使用生物标志物的各种方法本发明范围内的一些生物标志物是胆酸，甘油脱氧胆酸，甘氨胆酸，牛磺酸，3-羟基-2-乙基丙酸酯，4-咪唑乙酸酯，酪胺，邻氨基苯甲酸酯， 2'-脱氧胞苷，N-乙酰天冬氨酸（NAA），β-羟基己酸酯和肌氨酸（N-甲基甘氨酸）使用生物标志物的方法包括将第一肝细胞培养物暴露于测试试剂，并比较其中一种或多种 在第一肝细胞培养物中获得的更多生物标志物在没有测试剂的第二肝细胞培养物中获得的一种或多种生物标志物的水平，其中第一肝细胞培养物中的一种或多种生物标志物的差异水平与第二次肝细胞培养物中的水平相比 肝细胞培养表明试验剂是肝毒性剂。