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    Luminescent method of detecting soluble guanylate cyclase
    1.
    发明授权
    Luminescent method of detecting soluble guanylate cyclase 失效
    检测可溶性鸟苷酸环化酶的发光方法

    公开(公告)号：US06913898B2

    公开(公告)日：2005-07-05

    申请号：US10268533

    申请日：2002-10-10

    申请人： Ursula Schindler ,  Hartmut Strobel ,  Peter Schindler ,  Alexander Muelsch

    发明人： Ursula Schindler ,  Hartmut Strobel ,  Peter Schindler ,  Alexander Muelsch

    IPC分类号： G01N33/50 ,  C12Q1/32 ,  C12Q1/527 ,  C12Q1/66 ,  G01N21/78

    CPC分类号： C12Q1/527 ,  G01N2333/795 ,  G01N2500/00

    摘要： The invention relates to methods for detecting a soluble guanylate cyclase whose heme iron is in the trivalent oxidation state, and to methods for finding chemical substances which stimulate the activity of a soluble guanylate cyclase when the heme iron of at least part of this soluble guanylate cyclase is oxidized to the trivalent state and also to diagnostic aids or kits for detecting a soluble guanylate cyclase with trivalent heme iron. Further, the invention relates methods for detecting a soluble guanylate cyclase lacking a heme group, and to methods for finding chemical substances which stimulate the activity of a soluble guanylate cyclase lacking a heme group.

    摘要翻译： 本发明涉及用于检测其血红素铁处于三价氧化状态的可溶性鸟苷酸环化酶的方法，以及当该可溶性鸟苷酸环化酶的至少一部分的血红素铁时，发现刺激可溶性鸟苷酸环化酶活性的化学物质的方法 被氧化成三价状态，也用于用三价血红素铁检测可溶性鸟苷酸环化酶的诊断辅助剂或试剂盒。 此外，本发明涉及用于检测缺少血红素基团的可溶性鸟苷酸环化酶的方法，以及用于发现刺激缺少血红素基团的可溶性鸟苷酸环化酶的活性的化学物质的方法。

    Oxygenase enzymes and screening method
    2.
    发明申请
    Oxygenase enzymes and screening method 审中-公开
    加氧酶和筛选方法

    公开(公告)号：US20030207345A1

    公开(公告)日：2003-11-06

    申请号：US10453104

    申请日：2003-06-02

    申请人： California Institute of Technology

    发明人： Frances H. Arnold ,  Hyun Joo

    IPC分类号： C12Q001/26

    CPC分类号： C12N9/0071 ,  C07K2319/02 ,  C12N9/0065 ,  C12N9/0069 ,  C12N9/0077 ,  C12N15/102 ,  C12N15/1034 ,  C12N15/67 ,  C12N15/815 ,  C12Q1/26 ,  C12Q1/28 ,  G01N2333/795 ,  G01N2333/80 ,  G01N2333/90245

    摘要： A method for detecting the presence of an oxygenated compound which is produced when a substrate is reacted with an oxygenase for the substrate. The method involves reacting a coupling enzyme with the oxygenated compound to form a polymeric oxygenated compound which is fluorescent or luminescent. Measurement of the fluorescence or luminescence of the polymeric oxygenated compound provides indirect detection of the oxygenated compound produced by reaction of the oxygenase with the substrate. The method is carried out in a whole cell environment wherein the cell is transformed to express both the oxygenase being screened and the coupling enzyme. The method can be used to measure the activity of monooxygenases and dioxygenases on aromatic substrates. The method is amenable to large scale screening of enzyme mutants to isolate those with maximum oxygenase activity.

    摘要翻译： 用于检测当底物与用于底物的加氧酶反应时产生的含氧化合物的存在的方法。 该方法包括使偶联酶与含氧化合物反应以形成荧光或发光的聚合的氧化化合物。 聚合物氧化化合物的荧光或发光的测量提供了通过加氧酶与底物的反应产生的氧合化合物的间接检测。 该方法在整个细胞环境中进行，其中转化细胞以表达被筛选的加氧酶和偶联酶。 该方法可用于测量单加氧酶和双加氧酶在芳香族底物上的活性。 该方法适用于大规模筛选酶突变体以分离具有最大加氧酶活性的那些。

    Relative rates of cytochrome p450 metabolism
    3.
    发明授权
    Relative rates of cytochrome p450 metabolism 失效

    公开(公告)号：US06625547B1

    公开(公告)日：2003-09-23

    申请号：US09613875

    申请日：2000-07-10

    申请人： Kenneth R. Korzekwa ,  Jeffrey P. Jones

    发明人： Kenneth R. Korzekwa ,  Jeffrey P. Jones

    IPC分类号： G06G758

    CPC分类号： G06F19/16 ,  C12Q1/26 ,  G01N33/6803 ,  G01N2333/795 ,  G01N2333/80 ,  G01N2333/90245 ,  G06F19/12

    摘要： Reactive sites on a substrate molecule, typically a drug, may be identified and the relative rates of their metabolism by the CYP enzymes may be determined. Determining these relative rates is an important factor in determining the absolute rate of metabolism of the individual sites and the substrate molecule as a whole. This information is also a critical factor in determining whether and how the substrate can be redesigned to improve its ADME/PK properties. In this regard, it is particularly important to know how the relative rates compare to the rate of a non-metabolic side reaction (branch pathway) such as water generation and regeneration of the substrate.

    Method for detecting oxidized forms of soluble guanylate cyclase and a method for screening for activators of soluble guanylate cyclase having oxidized heme iron
    4.
    发明申请
    Method for detecting oxidized forms of soluble guanylate cyclase and a method for screening for activators of soluble guanylate cyclase having oxidized heme iron 失效
    用于检测可溶性鸟苷酸环化酶的氧化形式的方法和用于筛选具有氧化血红素铁的可溶性鸟苷酸环化酶活化剂的方法

    公开(公告)号：US20030054433A1

    公开(公告)日：2003-03-20

    申请号：US10268533

    申请日：2002-10-10

    申请人： Aventis Pharma Deutschland GmbH

    发明人： Ursula Schindler ,  Hartmut Strobel ,  Peter Schindler ,  Alexander Muelsch

    IPC分类号： C12Q001/26

    CPC分类号： C12Q1/527 ,  G01N2333/795 ,  G01N2500/00

    摘要： The invention relates to methods for detecting a soluble guanylate cyclase whose heme iron is in the trivalent oxidation state, and to methods for finding chemical substances which stimulate the activity of a soluble guanylate cyclase when the heme iron of at least part of this soluble guanylate cyclase is oxidized to the trivalent state and also to diagnostic aids or kits for detecting a soluble guanylate cyclase with trivalent heme iron. Further, the invention relates methods for detecting a soluble guanylate cyclase lacking a heme group, and to methods for finding chemical substances which stimulate the activity of a soluble guanylate cyclase lacking a heme group.

    摘要翻译： 本发明涉及用于检测其血红素铁处于三价氧化状态的可溶性鸟苷酸环化酶的方法，以及当该可溶性鸟苷酸环化酶的至少一部分的血红素铁时，发现刺激可溶性鸟苷酸环化酶活性的化学物质的方法 被氧化成三价状态，也用于用三价血红素铁检测可溶性鸟苷酸环化酶的诊断辅助剂或试剂盒。 此外，本发明涉及用于检测缺少血红素基团的可溶性鸟苷酸环化酶的方法，以及用于发现刺激缺少血红素基团的可溶性鸟苷酸环化酶的活性的化学物质的方法。

    Enzymes and metabolites involved in skatole metabolism
    5.
    发明授权
    Enzymes and metabolites involved in skatole metabolism 有权
    涉及粪土代谢的酶和代谢物

    公开(公告)号：US06448028B1

    公开(公告)日：2002-09-10

    申请号：US09672039

    申请日：2000-09-29

    申请人： E. James Squires ,  Gonzalo J. Diaz

    发明人： E. James Squires ,  Gonzalo J. Diaz

    IPC分类号： C12Q126

    CPC分类号： C12Q1/26 ,  A01K2217/05 ,  A01K2227/108 ,  C12N9/0008 ,  C12Q2600/156 ,  G01N2333/795 ,  G01N2333/80 ,  G01N2333/90245 ,  H01J49/04

    摘要： Novel metabolites and enzymes involved in skatole metabolism are disclosed. The novel metabolites are 3-OH-3-methylindolenine (HMI); 3-methyloxindole (3MOI); indole-3-carbinol (I-3C); and 2-aminoacetophenone (2-AM). Measuring levels of these metabolites in a pig may be useful in identifying the pig's ability to metabolize skatole and its susceptibility to boar taint. The novel enzymes involved in skatole metabolism are aldehyde oxidase and CYP2A6. Enhancing the activity of these enzymes may be useful in enhancing skatole metabolism and reducing boar taint. The identification of the enzyme also allows the development of screening assays for substances that interact with these enzymes and skatole metabolism. Pigs having high levels of these enzymes may be selected and bred to produce pigs that have a lower incidence of boar taint.

    摘要翻译： 公开了与代谢相关的新型代谢物和酶。 新型代谢物为3-OH-3-甲基多巴酚丁胺（HMI）; 3-甲氧基吲哚（3MOI）; 吲哚-3-甲醇（I-3C）; 和2-氨基苯乙酮（2-AM）。 测量猪中这些代谢物的含量可能有助于识别猪代谢粪便的能力及其对野猪污染的敏感性。 涉及粪臭素代谢的新型酶是醛氧化酶和CYP2A6。 提高这些酶的活性可能有助于增强粪便代谢和减少野猪污点。 酶的鉴定还允许开发与这些酶和粪便代谢相互作用的物质的筛选测定。 可以选择并培育具有高水平这些酶的猪，以产生具有较低的野猪污染发生率的猪。

    Prediction of diabetes impaired wound healing by urinary nitrate assay
    6.
    发明申请
    Prediction of diabetes impaired wound healing by urinary nitrate assay 有权

    公开(公告)号：US20010048915A1

    公开(公告)日：2001-12-06

    申请号：US09885410

    申请日：2001-06-21

    发明人： Joseph Boykin JR.

    IPC分类号： A61K049/00

    CPC分类号： G01N33/84 ,  G01N2333/795 ,  G01N2333/90245 ,  G01N2800/52 ,  Y10S514/866

    摘要： Wound healing is impaired in many diabetics, who suffer increased risk of chronic foot ulceration and amputation. Diabetic patients with poor healing ability were found to possess significantly lower fasting urinary nitrate levels than diabetic patients with normal healing ability or non-diabetic controls, implicating decreased endogenous nitric oxide activity as the mediator of diabetes-impaired wound healing. Methods and kits are provided for predicting the wound healing ability of diabetic patients based on the levels of nitric oxide related products such as nitrate or nitrite in urine or other specimens. Methods are also provided for treating non-wound healing diabetics and monitoring diabetic ulcer treatment.

    Method and apparatus for determining the role of cytochrome P450 and related enzymes in the metabolism of drugs and other chemicals
    8.
    发明授权
    Method and apparatus for determining the role of cytochrome P450 and related enzymes in the metabolism of drugs and other chemicals 失效
    用于确定细胞色素P450和相关酶在药物和其他化学物质代谢中的作用的方法和装置

    公开(公告)号：US5478723A

    公开(公告)日：1995-12-26

    申请号：US127317

    申请日：1993-09-27

    申请人： Andrew Parkinson ,  Dorn C. Cook

    发明人： Andrew Parkinson ,  Dorn C. Cook

    IPC分类号： C12Q1/26 ,  C12Q1/32 ,  C12Q1/00 ,  C12N9/02 ,  G01N33/483

    CPC分类号： C12Q1/32 ,  C12Q1/26 ,  G01N2333/795 ,  G01N2333/80 ,  G01N2333/90245 ,  G01N2500/00 ,  Y10S435/966 ,  Y10S530/846

    摘要： A method and apparatus for determining the enzyme or enzymes in the human body which metabolize a particular drug. Microsomes are obtained from each of several donors. The microsome for one donor is reacted with a test drug and the quantity of metabolites produced is determined. The microsomes are similarly each reacted with the test drug and the quantity of metabolites produced for each microsome is determined to generate drug metabolism data. The drug metabolism data obtained is compared to reference data which indicates the activity of a select number of major enzymes in each of the donors. The reference data for each enzyme is separately tabulated. The enzyme responsible for the metabolism of the test drug is identified when the metabolism data correlates with the tabulated reference data for that enzyme.

    摘要翻译： 用于测定代谢特定药物的人体内的酶或酶的方法和装置。 从几个供体中的每一个获得微粒体。 一个供体的微粒体与试验药物反应，并测定产生的代谢物的量。 微粒体同样地与试验药物反应，确定每个微粒体产生的代谢物的量以产生药物代谢数据。 将获得的药物代谢数据与参考数据进行比较，该参考数据指示每个供体中选择数量的主要酶的活性。 每个酶的参考数据单独列出。 当代谢数据与该酶的列表参考数据相关时，鉴定负责测试药物代谢的酶。