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1. 发明申请

WO2003014701A2 IMPROVED METHOD FOR MEASURING MEMBRANE POTENTIAL 审中-公开
标题翻译：用于测量膜电位的改进方法
公开(公告)号：WO2003014701A2
公开(公告)日：2003-02-20
申请号：PCT/US2002/025046
申请日：2002-08-07
申请人： MOLECULAR DEVICES CORPORATION , KLAUBERT, Dieter , DIWU, Zhenjun , YI, Guoliang , KIRK, Martin
发明人： KLAUBERT, Dieter , DIWU, Zhenjun , YI, Guoliang , KIRK, Martin
IPC分类号： G01N
CPC分类号： G01N33/52 , Y10S435/975
摘要： The invention encompasses an improved method for measuring membrane potential using compounds of the formula I as petentiometric probes. These probes may be used in combination with other fluorescent indicators such as Indo-1, Fura-2, and Fluo-3, such probes may be used in microplate reading devices such as FLIPR TR , fluorescent imaging plate reader, sold by Molecular Device Corp., of Sunnyvale, CA; flow cytometers; and fluorometers. Such probes are used to measure membrane potential in live cells. X is O. or S. n is 1 or 2.
摘要翻译：本发明包括使用式I化合物作为测量探针来测量膜电位的改进方法。这些探针可以与其他荧光指示剂如Indo-1，Fura-2和Fluo-3组合使用，这样的探针可以用于微孔板读取装置，例如FLIPR ，荧光成像读板器，由Molecular 加利福尼亚州桑尼维尔的Device Corp.; 流式细胞仪和荧光计。这种探针用于测量活细胞中的膜电位。 X是O.或S.n是1或2。

2. 发明申请

WO2003014701A3 POTENTIOMETRIC PROBE COMPOUNDS 审中-公开
公开(公告)号：WO2003014701A3
公开(公告)日：2003-02-20
申请号：PCT/US2002/025046
申请日：2002-08-07
申请人： MOLECULAR DEVICES CORPORATION , KLAUBERT, Dieter , DIWU, Zhenjun , YI, Guoliang , KIRK, Martin
发明人： KLAUBERT, Dieter , DIWU, Zhenjun , YI, Guoliang , KIRK, Martin
IPC分类号： C12Q1/02
摘要： The invention encompasses an improved method for measuring membrane potential using compounds of the formula I as petentiometric probes. These probes may be used in combination with other fluorescent indicators such as Indo-1, Fura-2, and Fluo-3, such probes may be used in microplate reading devices such as FLIPR TR , fluorescent imaging plate reader, sold by Molecular Device Corp., of Sunnyvale, CA; flow cytometers; and fluorometers. Such probes are used to measure membrane potential in live cells. X is O. or S. n is 1 or 2.

3. 发明申请

WO2013033515A1 COMPOUNDS AND METHODS FOR ASSAYING REDOX STATE OF METABOLICALLY ACTIVE CELLS AND METHODS FOR MEASURING NAD(P)/NAD(P)H 审中-公开
标题翻译：用于测定代谢活性细胞的氧化态的化合物和方法以及用于测量NAD（P）/ NAD（P）H的方法
公开(公告)号：WO2013033515A1
公开(公告)日：2013-03-07
申请号：PCT/US2012/053310
申请日：2012-08-31
申请人： PROMEGA CORPORATION , BENINK, Helene , CALI, James, J. , DUELLMAN, Sarah , KLAUBERT, Dieter , LEIPPE, Donna , O'BRIEN, Martha , SHULTZ, John , VIDUGIRIENE, Jolanta , ZHOU, Wenhui , SOBOL, Mary
发明人： BENINK, Helene , CALI, James, J. , DUELLMAN, Sarah , KLAUBERT, Dieter , LEIPPE, Donna , O'BRIEN, Martha , SHULTZ, John , VIDUGIRIENE, Jolanta , ZHOU, Wenhui , SOBOL, Mary
IPC分类号： C07D277/68 , C07D417/04 , C07D487/04 , C07D493/10 , G01N33/58 , C12Q1/66
CPC分类号： C12Q1/32 , C07D277/68 , C07D417/04 , C07D487/04 , C07D493/10 , C07D497/10 , C07F9/65583 , C07F9/6561 , C12Q1/66 , G01N21/763 , G01N33/5038 , G01N33/5735 , G01N33/582
摘要： The present invention provides compounds and methods for assaying redox state of metabolically active cells and methods for assaying enzyme activity and/or metabolite level by coupling to redox defining co-factor NAD(P)/NAD(P)H measurement.
摘要翻译：本发明提供了用于测定代谢活性细胞的氧化还原状态的化合物和方法以及通过与氧化还原定义的辅因子NAD（P）/ NAD（P）H测量偶联来测定酶活性和/或代谢物水平的方法。

4. 发明申请

WO2003066611A1 BIOLUMINESCENT PROTEASE ASSAY 审中-公开
标题翻译：生物发光蛋白质测定
公开(公告)号：WO2003066611A1
公开(公告)日：2003-08-14
申请号：PCT/US2003/002936
申请日：2003-01-31
申请人： PROMEGA CORPORATION , O'BRIAN, Martha , WOOD, Keith , KLAUBERT, Dieter , DAILY, Bill
发明人： O'BRIAN, Martha , WOOD, Keith , KLAUBERT, Dieter , DAILY, Bill
IPC分类号： C07D277/66
CPC分类号： C07D277/66 , C12Q1/37 , C12Q1/66
摘要： A sensitive bioluminescent assay to detect proteases including caspases, trypsin and tryptase is provided.
摘要翻译：提供了敏感的生物发光测定法来检测蛋白酶，包括胱天蛋白酶，胰蛋白酶和类胰蛋白酶。

5. 发明申请

WO2012030960A1 OXIDIZED GLUTATHIONE ASSAY 审中-公开
标题翻译：氧化谷物测定
公开(公告)号：WO2012030960A1
公开(公告)日：2012-03-08
申请号：PCT/US2011/049964
申请日：2011-08-31
申请人： PROMEGA CORPORATION , HUANG, Fen , KLAUBERT, Dieter , SHULTZ, John , ZHOU, Wenhui
发明人： HUANG, Fen , KLAUBERT, Dieter , SHULTZ, John , ZHOU, Wenhui
IPC分类号： C12Q1/26 , G01N33/566 , G01N33/573
CPC分类号： C12Q1/48 , G01N21/763 , G01N2333/91177
摘要： The present invention provides an assay for detection of oxidized glutathione (GSSG).
摘要翻译：本发明提供了氧化型谷胱甘肽（GSSG）的检测方法。

6. 发明申请

WO2004027378A2 LUMINESCENCE-BASED METHODS AND PROBES FOR MEASURING CYTOCHROME P450 ACTIVITY 审中-公开
标题翻译：用于测量细胞色素P450活性的基于发光的方法和探针
公开(公告)号：WO2004027378A2
公开(公告)日：2004-04-01
申请号：PCT/US2003/029078
申请日：2003-09-16
申请人： PROMEGA CORPORATION , CALI, James, J. , KLAUBERT, Dieter , DAILY, William , HO, Samuel, Kin, Sang , FRACKMAN, Susan , HAWKINS, Erika , WOOD, Keith, V.
发明人： CALI, James, J. , KLAUBERT, Dieter , DAILY, William , HO, Samuel, Kin, Sang , FRACKMAN, Susan , HAWKINS, Erika , WOOD, Keith, V.
IPC分类号： G01N
CPC分类号： G01N33/502 , A61K49/0008 , C07D417/04 , C12Q1/66 , G01N33/5088 , G01N33/582 , G01N2333/90245 , G01N2333/90251 , G01N2500/10
摘要： The present invention provides methods, compositions, substrates, and kits useful for analyzing the metabolic activity in cells, tissue, and animals and for screening test compounds for their effect on cytochrome P450 activity. In particular, a one-step and two-step methods using luminogenic molecules, e.g. luciferin or coelenterazines, that are cytochrome P450 substrates and that are also bioluminescent enzyme, e.g., luciferase, pro-substrates are provided. Upon addition of the luciferin derivative or other luminogenic molecule into a P450 reaction, the P450 enzyme metabolizes the molecule into a bioluminescent enzyme substrate, e.g., luciferin and/or luciferin derivative metabolite, in a P450 reaction. The resulting metabolite(s) serves as a substrate of the bioluminescent enzyme, e.g., luciferase, in a second lightgenerating reaction. Luminescent cytochrome P450 assays with low background signals and high sensitivity are disclosed and isoform selectivity is demonstrated. The present invention also provides an improved method for performing luciferase reactions which employs added pyrophosphatase to remove inorganic pyrophosphate, a luciferase inhibitor which may be present in the reaction mixture as a contaminant or may be generated during the reaction. The present method further provides a method for stabilizing and prolonging the luminescent signal in a luciferase-based assay using luciferase stabilizing agents such as reversible luciferase inhibitors.
摘要翻译：本发明提供了用于分析细胞，组织和动物中的代谢活性并筛选测试化合物对细胞色素P450活性的影响的方法，组合物，底物和试剂盒。特别地，使用发光分子的一步法和两步法，例如，荧光素或腔肠素，它们是细胞色素P450底物，也是生物发光酶，例如萤光素酶，原底物。在将荧光素衍生物或其他发光分子加入到P450反应中后，P450酶在P450反应中将该分子代谢成生物发光酶底物，例如荧光素和/或荧光素衍生物代谢物。产生的代谢物在第二次光照和害羞中作为生物发光酶的底物，例如萤光素酶，产生反应。公开了具有低背景信号和高灵敏度的发光细胞色素P450测定并证明了同种型选择性。本发明还提供了用于进行萤光素酶反应的改进方法，其使用添加的焦磷酸酶去除无机焦磷酸盐，荧光素酶抑制剂，其可以作为污染物存在于反应混合物中或可以在反应过程中产生。本发明方法进一步提供了使用荧光素酶稳定剂如可逆荧光素酶抑制剂在基于萤光素酶的测定中稳定和延长发光信号的方法。

7. 发明申请

WO2013025885A1 DETECTION OF HYDROGEN PEROXIDE 审中-公开
标题翻译：检测过氧化氢
公开(公告)号：WO2013025885A1
公开(公告)日：2013-02-21
申请号：PCT/US2012/051109
申请日：2012-08-16
申请人： PROMEGA CORPORATION , KLAUBERT, Dieter , SHULTZ, John , UNCH, James , VALLEY, Michael P. , WANG, Hui , ZHOU, Wenhui
发明人： KLAUBERT, Dieter , SHULTZ, John , UNCH, James , VALLEY, Michael P. , WANG, Hui , ZHOU, Wenhui
IPC分类号： A61K49/00 , C07F5/02
CPC分类号： C07F5/04 , C07D235/00 , C07D241/54 , C07D277/64 , C07F5/02 , C12Q1/66 , G01N33/5038 , G01N2500/10
摘要： The present invention provides compounds of formula (I), (II) or (III) wherein R 1 and R 11 are boronic acid or a borate ester useful for detection of hydrogen peroxide and methods of using same.
摘要翻译：本发明提供式（I），（II）或（III）的化合物，其中R 1和R 11为硼酸或可用于检测过氧化氢的硼酸酯及其使用方法。

8. 发明申请

WO2010021686A1 LUMINOGENIC COMPOUNDS AND METHODS TO DETECT CYTOCHROME P450 3A ENZYMES 审中-公开
标题翻译：荧光化合物和检测细胞色素P450 3A酶的方法
公开(公告)号：WO2010021686A1
公开(公告)日：2010-02-25
申请号：PCT/US2009/004696
申请日：2009-08-18
申请人： PROMEGA CORPORATION , KLAUBERT, Dieter , MEISENHEIMER, Poncho
发明人： KLAUBERT, Dieter , MEISENHEIMER, Poncho
IPC分类号： C07D277/68 , C07D417/04 , C07D417/14 , C12Q1/66
CPC分类号： C07D277/68 , C07D417/04 , C07D417/14 , C12Q1/26 , C12Q1/66 , G01N33/531
摘要： The present invention provides acetal derivatives of luciferin and methods for using such derivatives in enzyme activity assays where the luciferin derivative serves as a substrate for a desired enzyme and is a prosubstrate for luciferase (a proluciferin). Thus, by providing luciferin derivatives having a particular enzyme recognition site for a desired nonluciferase enzyme (a reactive chemical group in a molecule referred to as a substrate for the enzyme) coupled to the luciferin backbone (or other chemical moiety constituting a suitable substrate for luciferase), e.g., derivatives having modifications at the carboxyl group of D- luciferin or aminoluciferin as well as optionally other modifications, nonluciferase enzymes may be measured in a bioluminescent assay.
摘要翻译：本发明提供荧光素的缩醛衍生物和在酶活性测定中使用这些衍生物的方法，其中荧光素衍生物用作所需酶的底物，并且是萤光素酶（起始调素蛋白）的前体。因此，通过提供荧光素衍生物，其具有与所述荧光素主链（或构成荧光素酶的合适底物的其它化学部分）相连的所需非葡萄糖苷酶（分子中称为酶的底物的反应性化学基团）的酶识别位点），例如，可以在生物发光测定中测量在D-荧光素或氨基荧光素的羧基上具有修饰的衍生物以及任选的其它修饰，非变性酶。

9. 发明申请

WO2008118445A1 METHODS TO QUENCH LIGHT FROM OPTICAL REACTIONS 审中-公开
标题翻译：从光学反应中祛光的方法
公开(公告)号：WO2008118445A1
公开(公告)日：2008-10-02
申请号：PCT/US2008/003924
申请日：2008-03-26
申请人： PROMEGA CORPORATION , DAILY, William , HAWKINS, Erika , KLAUBERT, Dieter , MCDOUGALL, Mark , UNCH, James , WOOD, Keith V. , ZHOU, Wenhui , ZHU, Ji
发明人： DAILY, William , HAWKINS, Erika , KLAUBERT, Dieter , MCDOUGALL, Mark , UNCH, James , WOOD, Keith V. , ZHOU, Wenhui , ZHU, Ji
IPC分类号： C12Q1/66 , C07C211/30
CPC分类号： C12Q1/66
摘要： The present invention relates to single and dual reporter luminescence assays utilizing reagents to quench an optical, e.g., an enzyme-mediated luminescence, reaction. In one embodiment of the invention, a reagent is added to an assay which selectively quenches a first enzyme-mediated luminescence reaction without affecting a subsequent distinct enzyme-mediated luminescent reaction(s). An assay kit containing one or more selective quench reagents, and compositions comprising the quench reagent(s), are also provided.
摘要翻译：本发明涉及利用试剂猝灭光学（例如酶介导的发光）反应的单和双报告发光测定法。在本发明的一个实施方案中，将试剂加入到分析中，所述分析选择性猝灭第一酶介导的发光反应而不影响后续不同的酶介导的发光反应。还提供了含有一种或多种选择性猝灭试剂的测定试剂盒以及包含猝灭试剂的组合物。

10. 发明申请

WO2006093529A2 COVALENT TETHERING OF FUNCTIONAL GROUPS TO PROTEINS AND SUBSTRATES THEREFOR 审中-公开
标题翻译：功能组合对蛋白质和底物的共价分析
公开(公告)号：WO2006093529A2
公开(公告)日：2006-09-08
申请号：PCT/US2005/027307
申请日：2005-07-29
申请人： PROMEGA CORPORATION , DARZINS, Al , ENCELL, Lance , JOHNSON, Tonny , KLAUBERT, Dieter , LOS, Georgyi V. , MCDOUGALL, Mark , WOOD, Keith V. , WOOD, Monika G. , ZIMPRICH, Chad
发明人： DARZINS, Al , ENCELL, Lance , JOHNSON, Tonny , KLAUBERT, Dieter , LOS, Georgyi V. , MCDOUGALL, Mark , WOOD, Keith V. , WOOD, Monika G. , ZIMPRICH, Chad
IPC分类号： C07K14/47 , C12N9/14 , C12Q1/26
CPC分类号： C12N9/14 , B82Y5/00 , B82Y10/00 , B82Y30/00 , C07K2299/00 , C12N9/0069 , C12Q1/26 , C12Q1/34 , C12Q1/66 , C12Y113/12005 , C12Y308/01005
摘要： A mutant hydrolase optionally fused to a protein of interest is provided. The mutant hydrolase is capable of forming a bond with a substrate for the corresponding nonmutant (wild-type) hydrolase which is more stable than the bond formed between the wild-type hydrolase and the substrate and has at least two amino acid substitutions relative to the wild-type hydrolase. Substrates for hydrolases comprising one or more functional groups are also provided, as well as methods of using the mutant hydrolase and the substrates of the invention. Also provided is a fusion protein capable of forming a stable bond with a substrate and cells which express the fusion protein.
摘要翻译：提供任选融合到感兴趣的蛋白质的突变体水解酶。突变水解酶能够与相应的非突变（野生型）水解酶的底物形成键，其比野生型水解酶和底物之间形成的键更稳定，并且相对于野生型水解酶具有至少两个氨基酸取代野生型水解酶。还提供了包含一个或多个官能团的水解酶的底物，以及使用本发明的突变型水解酶和底物的方法。还提供能够与底物形成稳定结合的融合蛋白和表达融合蛋白的细胞。

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