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公开(公告)号:US6114350A
公开(公告)日:2000-09-05
申请号:US294678
申请日:1999-04-19
申请人: Malcolm Harry Randall , Philip Richard Buzby , Thomas Joseph Erickson , Joseph David Trometer , Joseph John Miller, Jr. , David George Ahern , Mark Norman Bobrow
发明人: Malcolm Harry Randall , Philip Richard Buzby , Thomas Joseph Erickson , Joseph David Trometer , Joseph John Miller, Jr. , David George Ahern , Mark Norman Bobrow
IPC分类号: G01N33/533 , A61K49/00 , C07D209/08 , C09B23/00 , C09K11/06 , A61K31/47 , A61K31/425 , C07D215/04 , C07D277/60 , C07D279/16
CPC分类号: A61K49/0021 , A61K49/0032 , A61K49/0052 , A61K49/0056 , C07D209/08
摘要: A cyanine dye having the formula ##STR1## wherein R.sub.1 -R.sub.8 are each independently selected from a group consisting of hydrogen, C.sub.1 -C.sub.6 alkyl group, and C.sub.0 -C.sub.4 alkyl group having a hydrophilic substituent thereon. R.sub.11 and R.sub.12 are chosen to include a free or protected thiol, amine or hydroxyl substituent capable of reacting with a target molecule through a nucleophilic displacement mechanism. The dye is useful in labeling a variety of target molecules. Processes are described for synthesizing suitable heterocyclic and indole derivatives as precursors for the aforementioned cyanine dyes.
摘要翻译: 具有下式的花青染料其中R 1 -R 8各自独立地选自氢,C 1 -C 6烷基和在其上具有亲水取代基的C 0 -C 4烷基。 R11和R12被选择为包括能够通过亲核置换机理与靶分子反应的游离或保护的硫醇,胺或羟基取代基。 该染料可用于标记各种靶分子。 描述了合成合适的杂环和吲哚衍生物作为前述花青染料的前体的方法。
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公开(公告)号:US06204389B1
公开(公告)日:2001-03-20
申请号:US09448241
申请日:1999-11-24
申请人: Malcolm Harry Randall , Philip Richard Buzby , Thomas Joseph Erickson , Joseph David Trometer , Joseph John Miller, Jr. , David George Ahern , Mark Norman Bobrow
发明人: Malcolm Harry Randall , Philip Richard Buzby , Thomas Joseph Erickson , Joseph David Trometer , Joseph John Miller, Jr. , David George Ahern , Mark Norman Bobrow
IPC分类号: C07D27904
CPC分类号: A61K49/0021 , A61K49/0032 , A61K49/0052 , A61K49/0056 , C07D209/08
摘要: A cyanine dye having the formula wherein R1--R8 are each independently selected from a group consisting of hydrogen, C1-C6 alkyl group, and C0-C4 alkyl group having a hydrophilic substituent thereon. R11 and R12 are chosen to include a free or protected thiol, amine or hydroxyl substituent capable of reacting with a target molecule through a nucleophilic displacement mechanism. The dye is useful in labeling a variety of target molecules. Processes are described for synthesizing suitable heterocyclic and indole derivatives as precursors for the aforementioned cyanine dyes.
摘要翻译: 具有式R 1 -R 8的花青染料各自独立地选自氢,C 1 -C 6烷基和在其上具有亲水取代基的C 0 -C 4烷基。 R11和R12被选择为包括能够通过亲核置换机理与靶分子反应的游离或保护的硫醇,胺或羟基取代基。 该染料可用于标记各种靶分子。 描述了合成合适的杂环和吲哚衍生物作为前述花青染料的前体的方法。
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公开(公告)号:US06197956B1
公开(公告)日:2001-03-06
申请号:US09449333
申请日:1999-11-24
申请人: Malcolm Harry Randall , Philip Richard Buzby , Thomas Joseph Erickson , Joseph David Trometer , Joseph John Miller, Jr. , David George Ahern , Mark Norman Bobrow
发明人: Malcolm Harry Randall , Philip Richard Buzby , Thomas Joseph Erickson , Joseph David Trometer , Joseph John Miller, Jr. , David George Ahern , Mark Norman Bobrow
IPC分类号: C07D27916
CPC分类号: A61K49/0021 , A61K49/0032 , A61K49/0052 , A61K49/0056 , C07D209/08
摘要: A cyanine dye having the formula wherein R1-R8 are each independently selected from a group consisting of hydrogen, C1-C6 alkyl group, and C0-C4 alkyl group having a hydrophilic substituent thereon. R11 and R12 are chosen to include a free or protected thiol, amine or hydroxyl substituent capable of reacting with a target molecule through a nucleophilic displacement mechanism. The dye is useful in labeling a variety of target molecules. Processes are described for synthesizing suitable heterocyclic and indole derivatives as precursors for the aforementioned cyanine dyes.
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公开(公告)号:US06437141B2
公开(公告)日:2002-08-20
申请号:US09824316
申请日:2001-04-02
申请人: Malcolm Harry Randall , Philip Richard Buzby , Thomas Joseph Erickson , Joseph David Trometer , Joseph John Miller, Jr. , David George Ahern , Mark Norman Bobrow
发明人: Malcolm Harry Randall , Philip Richard Buzby , Thomas Joseph Erickson , Joseph David Trometer , Joseph John Miller, Jr. , David George Ahern , Mark Norman Bobrow
IPC分类号: C07D27904
CPC分类号: A61K49/0021 , A61K49/0032 , A61K49/0052 , A61K49/0056 , C07D209/08
摘要: A cyanine dye having the formula wherein R1-R8 are each independently selected from a group consisting of hydrogen, C1-C6 alkyl group, and C0-C4 alkyl group having a hydrophilic substituent thereon. R11 and R12 are chosen to include a free or protected thiol, amine or hydroxyl substituent capable of reacting with a target molecule through a nucleophilic displacement mechanism. The dye is useful in labeling a variety of target molecules. Processes are described for synthesizing suitable heterocyclic and indole derivatives as precursors for the aforementioned cyanine dyes.
摘要翻译: 具有化学式R 1 -R 8的花青染料各自独立地选自氢,C 1 -C 6烷基和在其上具有亲水取代基的C 0 -C 4烷基。 R11和R12被选择为包括能够通过亲核置换机理与靶分子反应的游离或保护的硫醇,胺或羟基取代基。 该染料可用于标记各种靶分子。 描述了合成合适的杂环和吲哚衍生物作为前述花青染料的前体的方法。
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公开(公告)号:US06224644B1
公开(公告)日:2001-05-01
申请号:US09448242
申请日:1999-11-24
申请人: Malcolm Harry Randall , Philip Richard Buzby , Thomas Joseph Erickson , Joseph David Trometer , Joseph John Miller, Jr. , David George Ahern , Mark Norman Bobrow
发明人: Malcolm Harry Randall , Philip Richard Buzby , Thomas Joseph Erickson , Joseph David Trometer , Joseph John Miller, Jr. , David George Ahern , Mark Norman Bobrow
IPC分类号: C07D27904
CPC分类号: A61K49/0021 , A61K49/0032 , A61K49/0052 , A61K49/0056 , C07D209/08
摘要: A cyanine dye having the formula wherein R1-R8 are each independently selected from a group consisting of hydrogen, C1-C6 alkyl group, and C0-C4 alkyl group having a hydrophilic substituent thereon. R11 and R12 are chosen to include a free or protected thiol, amine or hydroxyl substituent capable of reacting with a target molecule through a nucleophilic displacement mechanism. The dye is useful in labeling a variety of target molecules. Processes are described for synthesizing suitable heterocyclic and indole derivatives as precursors for the aforementioned cyanine dyes.
摘要翻译: 具有化学式R 1 -R 8的花青染料各自独立地选自氢,C 1 -C 6烷基和在其上具有亲水取代基的C 0 -C 4烷基。 R11和R12被选择为包括能够通过亲核置换机理与靶分子反应的游离或保护的硫醇,胺或羟基取代基。 该染料可用于标记各种靶分子。 描述了合成合适的杂环和吲哚衍生物作为前述花青染料的前体的方法。
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公开(公告)号:US5767287A
公开(公告)日:1998-06-16
申请号:US869032
申请日:1997-06-04
IPC分类号: G01N33/533 , C07D209/14 , C09B23/00 , C09B23/02 , G01N21/78 , C07D209/08
CPC分类号: C09B23/02 , C07D209/14
摘要: Novel intermediates having an indolenine nucleus which are useful in the synthesis of fluorescent sulfoindocyanine dyes are described. Dyes synthesized using such intermediates do not contain a reactive group that will covalently attach to a target molecule at an amine- or hydroxy-containing site. Rather, these intermediates are linked to an enzyme substrate or a member of a specific binding pair. Also included are tyramide-containing sulfonidocyanine dyes.
摘要翻译: 描述了可用于合成荧光磺基吲哚菁染料的具有吲哚宁核的新型中间体。 使用这种中间体合成的染料不含有将在含胺或羟基的位点共价连接到靶分子上的反应性基团。 相反,这些中间体连接到酶底物或特异性结合对的成员。 还包括含有酪酰胺的磺胺蓝染料。
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公开(公告)号:US5688966A
公开(公告)日:1997-11-18
申请号:US687853
申请日:1996-07-26
IPC分类号: G01N33/533 , C07D209/14 , C09B23/00 , C09B23/02 , G01N21/78 , C07D403/06
CPC分类号: C09B23/02 , C07D209/14
摘要: Novel intermediates having an indolenine nucleus which are useful in the synthesis of fluorescent sulfoindocyanine dyes are described. Dyes synthesized using such intermediates do not contain a reactive group that will covalently attach to a target molecule at an amine- or hydroxy-containing site. Rather, these intermediates are linked to an enzyme substrate or a member of a specific binding pair. Also included are tyramide-comaining sulfonidocyanine dyes.
摘要翻译: 描述了可用于合成荧光磺基吲哚菁染料的具有吲哚宁核的新型中间体。 使用这种中间体合成的染料不含有将在含胺或羟基的位点共价连接到靶分子上的反应性基团。 相反,这些中间体连接到酶底物或特异性结合对的成员。 还包括酪酰胺接枝磺胺蓝染料。
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公开(公告)号:US20090253117A1
公开(公告)日:2009-10-08
申请号:US12403790
申请日:2009-03-13
申请人: Blas Cerda , Mark Norman Bobrow
发明人: Blas Cerda , Mark Norman Bobrow
CPC分类号: C12Q1/34 , C07C237/22 , C07H15/203 , C07K5/06 , C07K19/00 , G01N2333/924 , G01N2458/15
摘要: An inventive substrate is provided which includes a substrate compound of formula A-B1-B2-B3-B4: wherein A is a sugar moiety; B1 is a linker moiety allowing the conjugation of moiety A and the remaining structure of the substrate; B2 is a linker moiety with a free reactive amino group so as to be available for reaction with carboxylic acids or detectable tags; B3 contains a permanently charged element such as a quaternary ammonium group so as to increase sensitivity for mass spectrometry analysis; and B4 of various carbon length conferring specificity amongst individual substrates in detection methods. Also provided is a molecule of the formula B1-B2-B3-B4, with similar structural characteristics to an enzymatic product produced by the action of a target enzyme on an inventive substrate. Further provided are methods for using inventive substrates for detecting enzymatic activity.
摘要翻译: 提供了本发明的底物,其包括式A-B1-B2-B3-B4的底物化合物:其中A是糖部分; B1是连接部分,允许部分A与底物的剩余结构共轭; B2是具有游离反应性氨基的接头部分,以便可用于与羧酸或可检测标签反应; B3含有永久带电元件如季铵基,以提高质谱分析的灵敏度; 和各种碳长度的B4在检测方法中在各个底物之间赋予特异性。 还提供了式B1-B2-B3-B4的分子,其与通过靶酶在本发明底物上的作用产生的酶产物具有相似的结构特征。 还提供了使用本发明的底物检测酶活性的方法。
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公开(公告)号:US06372937B1
公开(公告)日:2002-04-16
申请号:US09434742
申请日:1999-11-05
IPC分类号: C07C22900
CPC分类号: C12Q1/28 , C07C235/20
摘要: A method for enhancing the conversion of a phenol substrate to a product by a peroxidase enzyme comprises the steps of reacting a conjugate comprising a detectably labeled phenol with a peroxidase enzyme in the presence of an enhancing reagent, the enhancing reagent conmprising an inorganic salt, an organic compound having the formula wherein when X is B(OH)2, Y is I, or wherein when X is OH, Y is a halogen, or Q-R wherein Q is a linear or branched 1-12 heteroatom alkyl wherein the heteroatoms are selected from C, N, O, and S, wherein the bonds connecting the heteroatom alkyl chain are single or double, wherein any carbon atom in the heteroatom alkyl chain optionally includes a substituent selected from —OH, —COOH, —NH2, and —SH, and wherein R is selected from —OH, —COOH, —NH2, and —CH3; or mixtures of the inorganic salt and the organic compound. A compound having the formula: wherein R1 is —CH2OH, —COOH, and n is 1-8.
摘要翻译: 通过过氧化物酶增强酚底物向产物的转化的方法包括以下步骤:在增强试剂存在下使包含可检测标记的苯酚的缀合物与过氧化物酶反应,使无机盐, 当X为B(OH)2,Y为I时,或其中当X为OH时,Y为卤素或QR为有机化合物,其中Q为直链或支链1-12杂原子烷基,其中杂原子选自 C,N,O和S,其中连接杂原子烷基链的键是单或双键,其中杂原子烷基链中的任何碳原子任选地包括选自-OH,-COOH,-NH 2和-SH的取代基, 并且其中R选自-OH,-COOH,-NH 2和-CH 3; 或无机盐和有机化合物的混合物。 具有下式的化合物:其中R 1是-CH 2 OH,-COOH,n是1-8。
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公开(公告)号:US06399299B1
公开(公告)日:2002-06-04
申请号:US09430429
申请日:1999-10-29
IPC分类号: C12Q168
CPC分类号: G01N33/54306 , C12Q1/6837 , C12Q2563/125
摘要: The present invention concerns an array-based analytical system and method having an enhanced sensitivity which allows for simple and rapid analysis of relative unmodified samples which comprises an analytical system of the type having a plurality of different first members of a specific binding pair affixed in an array thereupon, a mixture including at least one second member of a specific binding pair capable of binding to one of the first members so as to form a specific binding pair which is affixed to the support member, and a reporter system that produces a detectable signal indicative of the presence of the specific binding pair on the support member and wherein the reporter system includes an amplified reporter system that is independent of layering.
摘要翻译: 本发明涉及一种基于阵列的分析系统和方法,其具有增强的灵敏度,其允许相对未修改的样品的简单和快速分析,其包括具有多个不同的第一成员的分析系统,所述第一成员固定在 阵列,其包含至少一个能够结合到第一个成员之一的特异性结合对的第二个成员的混合物,以形成固定在支持部件上的特异性结合对,以及产生可检测信号的报告系统 指示在支持构件上存在特异性结合对,并且其中报告系统包括独立于分层的扩增报告系统。
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