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    Substrate probe for use in measuring enzyme activity
    1.
    发明授权
    Substrate probe for use in measuring enzyme activity 有权
    用于测量酶活性的底物探针

    公开(公告)号：US08481254B2

    公开(公告)日：2013-07-09

    申请号：US12675511

    申请日：2008-09-08

    申请人： Fumio Yamauchi ,  Kimihiro Yoshimura ,  Katsuaki Kuge ,  Tetsuya Yano ,  Masahiro Shirakawa ,  Yasuhiro Aoyama ,  Shinsuke Sando

    发明人： Fumio Yamauchi ,  Kimihiro Yoshimura ,  Katsuaki Kuge ,  Tetsuya Yano ,  Masahiro Shirakawa ,  Yasuhiro Aoyama ,  Shinsuke Sando

    IPC分类号： C12Q1/00

    CPC分类号： C12Q1/54 ,  C12Q1/32 ,  C12Q1/34 ,  G01N24/088 ,  G01R33/281 ,  G01R33/4633 ,  G01R33/465 ,  G01R33/483 ,  G01R33/5601 ,  Y02P20/582

    摘要： Substrate probe capable of detecting enzyme activity with high accuracy and a method for detecting the enzyme activity by a multi nuclear magnetic resonance method using the substrate probe. Multi-dimensional nuclear magnetic resonance is performed by using a substrate probe, which is used for measuring enzyme activity by a multi-dimensional nuclear magnetic resonance method and characterized by containing a enzyme recognition site that is selectively recognized by an active-state enzyme, as at least one constitutional unit, and a group to which at least three nuclear magnetic resonance active nuclei each having a nuclear spin and a different resonance frequency are connected, being present specifically to the enzyme recognition, thereby detecting presence of the substrate probe and the enzyme activity. Alternatively, imaging of the enzyme activity is performed by a multi-dimensional nuclear resonance imaging method.

    摘要翻译： 能够高精度地检测酶活性的底物探针和使用底物探针的多核磁共振法检测酶活性的方法。 通过使用用于通过多维核磁共振法测定酶活性的底物探针进行多维核磁共振，其特征在于含有被活性酶选择性识别的酶识别位点作为 至少一个结构单元和至少三个具有核自旋和不同共振频率的核磁共振活性核连接的基团，其特异性地存在于酶识别中，从而检测底物探针和酶的存在 活动。 或者，通过多维核共振成像方法进行酶活性的成像。

    MULTISITE PHOSPHORYLATED PEPTIDE (PROTEIN) RECOGNIZING COMPOUND AND DETECTION METHOD, IMAGING METHOD, ALZHEIMER'S DISEASE DIAGNOSING METHOD AND REAGENT KIT USING THE SAME
    8.
    发明申请
    MULTISITE PHOSPHORYLATED PEPTIDE (PROTEIN) RECOGNIZING COMPOUND AND DETECTION METHOD, IMAGING METHOD, ALZHEIMER'S DISEASE DIAGNOSING METHOD AND REAGENT KIT USING THE SAME 有权
    多肽磷酸化肽（蛋白质）识别化合物和检测方法，成像方法，阿尔茨海默病的诊断方法和使用该试剂的试剂盒

    公开(公告)号：US20090233373A1

    公开(公告)日：2009-09-17

    申请号：US12393011

    申请日：2009-02-25

    申请人： Itaru Hamachi ,  Fumio Yamauchi ,  Tetsuya Yano ,  Kimihiro Yoshimura ,  Akio Ojida ,  Takashi Sakamoto ,  Masaaki Inoue

    发明人： Itaru Hamachi ,  Fumio Yamauchi ,  Tetsuya Yano ,  Kimihiro Yoshimura ,  Akio Ojida ,  Takashi Sakamoto ,  Masaaki Inoue

    IPC分类号： G01N33/68 ,  C07D213/02 ,  C07F3/06 ,  C07F5/02

    CPC分类号： C07F5/022 ,  C07D207/335 ,  C07D401/14 ,  G01N33/6842 ,  Y10T436/16 ,  Y10T436/163333

    摘要： There are provided a novel compound which captures a multisite phosphorylated peptide or protein specifically to a phosphorylation site and a method for detecting a multisite phosphorylated peptide or protein using the same. In particular, there are provided a compound which specifically detects an excessively phosphorylated tau protein observed in the brain affected by Alzheimer's disease and a method for diagnosing Alzheimer's disease in vitro or in vivo using the compound. By bringing a metal complex compound having two dipicolylamine (Dpa) moieties and a spacer including a chromogenic or luminescent functional group or atom group into contact with a multisite phosphorylated peptide or protein, the compound recognizes the distance between phosphate groups and specifically binds to the peptide or the protein, and a multisite phosphorylated peptide or protein or a kinase activity is optically detected by measuring the change, or a multisite phosphorylated peptide or protein or kinase activity is imaged by an optical imaging method applying the change in the luminescence.

    摘要翻译： 提供了一种新颖的化合物，其特异性捕获磷酸化位点的多位点磷酸化肽或蛋白质，以及使用该化合物检测多位点磷酸化肽或蛋白质的方法。 特别地，提供了特异性检测在受阿尔茨海默氏病影响的脑中观察到的过度磷酸化的tau蛋白的化合物和使用该化合物在体外或体内诊断阿尔茨海默病的方法。 通过使具有两个二聚苯基胺（Dpa）部分的金属配位化合物和包含显色或发光官能团或原子基团的间隔基与多位点磷酸化肽或蛋白质接触，该化合物识别磷酸基团之间的距离并特异性结合肽 或蛋白质，以及多位点磷酸化肽或蛋白质或激酶活性通过测量变化进行光学检测，或者通过应用发光变化的光学成像方法对多位点磷酸化肽或蛋白质或激酶活性进行成像。

    Multisite phosphorylated peptide (protein) recognizing compound and detection method, imaging method, alzheimer's disease diagnosing method and reagent kit using the same
    9.
    发明授权
    Multisite phosphorylated peptide (protein) recognizing compound and detection method, imaging method, alzheimer's disease diagnosing method and reagent kit using the same 有权
    多位点磷酸化肽（蛋白质）识别化合物和检测方法，成像方法，阿尔茨海默病诊断方法和使用该方法的试剂盒

    公开(公告)号：US08093060B2

    公开(公告)日：2012-01-10

    申请号：US12393011

    申请日：2009-02-25

    申请人： Itaru Hamachi ,  Fumio Yamauchi ,  Tetsuya Yano ,  Kimihiro Yoshimura ,  Akio Ojida ,  Takashi Sakamoto ,  Masaaki Inoue

    发明人： Itaru Hamachi ,  Fumio Yamauchi ,  Tetsuya Yano ,  Kimihiro Yoshimura ,  Akio Ojida ,  Takashi Sakamoto ,  Masaaki Inoue

    IPC分类号： G01N33/48

    CPC分类号： C07F5/022 ,  C07D207/335 ,  C07D401/14 ,  G01N33/6842 ,  Y10T436/16 ,  Y10T436/163333

    摘要： A compound which captures a multisite phosphorylated peptide or protein specifically to a phosphorylation site and a method for detecting the peptide or protein using the compound. Particularly, a compound which specifically detects an excessively phosphorylated tau protein observed in the brain affected by Alzheimer's disease and a method for diagnosing Alzheimer's disease in vitro or in vivo using the compound are provided. By bringing a metal complex compound having two dipicolylamine (Dpa) moieties and a spacer including a chromogenic or luminescent functional or atom group into contact with a multisite phosphorylated peptide or protein, the compound recognizes the distance between phosphate groups and specifically binds to the peptide or protein, and a multisite phosphorylated peptide or protein or kinase activity is optically detected by measuring the change, or a multisite phosphorylated peptide or protein or kinase activity is imaged by an optical imaging method applying the change in luminescence.

    摘要翻译： 捕获特异性磷酸化位点的多位点磷酸化肽或蛋白质的化合物和使用该化合物检测肽或蛋白质的方法。 特别地，提供了特异性检测在受阿尔茨海默氏病影响的脑中观察到的过度磷酸化的tau蛋白的化合物以及使用该化合物在体外或体内诊断阿尔茨海默病的方法。 通过使具有两个二苯基胺（Dpa）部分的金属络合物和包含显色或发光官能团或原子基团的间隔基与多位点磷酸化肽或蛋白质接触，化合物识别磷酸基团之间的距离，并特异性结合肽或 蛋白质和多位点磷酸化肽或蛋白质或激酶活性通过测量变化来光学检测，或者通过应用发光变化的光学成像方法对多位点磷酸化肽或蛋白质或激酶活性进行成像。