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1. 发明授权

US06451531B1 Dioxetane labeled probes and detection assays employing the same 有权
标题翻译：二氧杂环丁烷标记的探针和使用其的检测测定
公开(公告)号：US06451531B1
公开(公告)日：2002-09-17
申请号：US09340726
申请日：1999-06-29
申请人： Irena Bronstein , Brooks Edwards , Christopher Martin , John Voyta
发明人： Irena Bronstein , Brooks Edwards , Christopher Martin , John Voyta
IPC分类号： C12Q168
CPC分类号： C07H21/00 , C07D321/00 , C12Q1/6816 , C12Q1/686 , Y02P20/55 , C12Q2561/101 , C12Q2565/113
摘要： Probes labeled with 1,2-dioxetane precursors can be employed in a variety of assays. The probes may be nucleic acid, peptide nucleic acid, proteins including enzyme, antibody or antigen, steroid, carbohydrate, drug or non-drug hapten. The probe is provided with a 1,2-dioxetane precursor bound thereto, generally either covalently, or a strong ligand bond. The dioxetane precursor moiety is converted to a bound 1,2-dioxetane by exposure to singlet oxygen. These dioxetane (labels) either spontaneously decompose, or are induced to decompose by an appropriate trigger to release light. The trigger may be a change in pH temperature, or an agent which removes a protective group. Assay formats in which these 1,2-dioxetane labeled probes and referents may be used to include hybridization assays, immuno assays, gel-based assays and Capillary Zone Electrophoresis.
摘要翻译：用1,2-二氧杂环丁烷前体标记的探针可用于多种测定。探针可以是核酸，肽核酸，蛋白质，包括酶，抗体或抗原，类固醇，碳水化合物，药物或非药物半抗原。探针具有与其结合的1,2-二氧杂环丁烷前体，通常共价或强配体键。通过暴露于单线态氧将二氧杂环丁烷前体部分转化为结合的1,2-二氧环乙烷。这些二氧杂环丁烷（标记）会自发分解，或被适当的触发剂诱导分解以释放光。触发可能是pH温度的变化，或者是除去保护基团的试剂。这些1,2-二氧杂环丁烷标记的探针和指示物可用于包括杂交测定，免疫测定，基于凝胶的测定和毛细管区域电泳的测定形式。

2. 发明授权

US06355441B1 Benzothiazole dioxetanes 有权
标题翻译：苯并噻唑二氧杂环丁烷
公开(公告)号：US06355441B1
公开(公告)日：2002-03-12
申请号：US09362047
申请日：1999-07-28
申请人： Brooks Edwards , Irena Bronstein
发明人： Brooks Edwards , Irena Bronstein
IPC分类号： G01N3353
CPC分类号： C07D277/62 , C07D417/04 , C07D493/04 , C07F9/65512 , C07F9/65586 , G01N33/582 , Y10S530/807
摘要： Chemiluminescent 1,2-dioxetane compounds capable of producing light energy when decomposed, substantially stable at room temperature, represented by the formulas I or II:
摘要翻译：化学发光的1,2-二氧杂环丁烷化合物，当分解时能够产生光能，在室温下基本稳定，由式I或II表示：

3. 发明授权

US5869699A 1,2 chemiluminescent dioxetanes of improved performance 失效
公开(公告)号：US5869699A
公开(公告)日：1999-02-09
申请号：US871963
申请日：1997-06-10
申请人： Irena Bronstein , Brooks Edwards , Alison Sparks
发明人： Irena Bronstein , Brooks Edwards , Alison Sparks
IPC分类号： C07D321/00 , C07F9/655 , C07G3/00 , C12Q1/37 , G01N33/58 , C07F9/28 , C07D305/14
CPC分类号： G01N33/582 , C07D321/00 , C07F9/65512 , C07G3/00 , C12Q1/37 , Y02P20/55
摘要： A new class of stable dioxetanes bears a polycyclic stabilizing group and aryloxy moiety, the oxygen atom of which is provided with a protective group which can be removed by an enzymatic or chemical trigger admixed with the dioxetane. The polycyclic stabilizing group is preferably spiroadamantane. The group further bears an alkoxy, aryloxy, aralkyloxy or cycloalkyloxy moiety which is partially or completely substituted with halogens, particularly fluorine and chlorine. Proper selection of electron active groups on the stabilizing moiety, the aryl group and the OR group yields enhanced enzyme kinetics, superior light intensity and excellent detection sensitivity in various assays.

4. 发明授权

US5851771A Chemiluminescent 1,2-dioxetanes 失效
公开(公告)号：US5851771A
公开(公告)日：1998-12-22
申请号：US588810
申请日：1996-01-19
申请人： Irena Bronstein , Brooks Edwards , Alison Sparks
发明人： Irena Bronstein , Brooks Edwards , Alison Sparks
IPC分类号： G01N33/532 , A43B3/00 , C07C43/178 , C07C43/196 , C07C43/215 , C07C43/225 , C07C43/23 , C07C43/315 , C07C45/67 , C07C47/565 , C07C47/575 , C07C65/03 , C07C65/21 , C07C69/00 , C07C69/017 , C07C69/24 , C07C69/78 , C07C69/84 , C07C69/92 , C07C205/06 , C07C205/37 , C07C205/44 , C07C217/84 , C07C233/18 , C07C233/75 , C07C271/28 , C07C271/58 , C07C309/75 , C07C311/04 , C07C311/08 , C07C311/16 , C07D321/00 , C07F7/08 , C07F7/18 , C07F9/12 , C07F9/40 , C07F9/655 , C07F9/6574 , C07G3/00 , C07H15/203 , C07H15/26 , C12Q1/34 , C12Q1/37 , C12Q1/42 , C12Q1/68 , G01N21/76 , G01N21/78 , G01N33/52 , G01N33/535 , G01N33/58
CPC分类号： G01N33/582 , A43B1/0036 , A43B1/0072 , A43B3/0031 , C07C205/37 , C07C205/44 , C07C217/84 , C07C233/18 , C07C271/28 , C07C271/58 , C07C43/1788 , C07C43/196 , C07C43/215 , C07C43/225 , C07C43/23 , C07C43/315 , C07C45/673 , C07C47/565 , C07C47/575 , C07C65/03 , C07C65/21 , C07D321/00 , C07F9/12 , C07F9/4056 , C07F9/65512 , C07F9/65742 , C07G3/00 , C07H15/203 , C07H15/26 , C12Q1/34 , C12Q1/37 , C12Q1/42 , G01N21/76 , G01N33/581 , C07C2103/74 , C12Q2334/00 , Y10S435/81 , Y10S435/975
摘要： Spiroadamantyl dioxetanes bearing an alkoxy substituent, and an aromatic substituent of phenyl or naphthyl on the dioxetane ring can be activated to chemiluminesce if the aromatic substituent bears a moiety designated OX, wherein the X is cleaved by an enzyme with which the dioxetane is permitted to come in contact with. The T.sub.1/2 kinetics of the chemiluminescent reaction, as well as the signal intensity, or quantum yield of the chemiluminescent reaction, can be altered by selection of an electron-withdrawing or an electron-donating group Z, at positions on the aromatic substituent other than those adjacent the point of attachment to the dioxetane. Signal strength can further be enhanced by recognized chemiluminescent enhancers.

5. 发明授权

US5679803A 1,2 chemiluminescent dioxetanes of improved performance 失效
标题翻译： 1,2化学发光二恶烷具有改进的性能
公开(公告)号：US5679803A
公开(公告)日：1997-10-21
申请号：US547372
申请日：1995-10-25
申请人： Irena Bronstein , Brooks Edwards
发明人： Irena Bronstein , Brooks Edwards
IPC分类号： C07D305/14 , C07D321/00 , C07F9/06 , C07F9/655 , C07G3/00 , C12Q1/37 , G01N33/58 , C07F7/02
CPC分类号： C07D321/00 , C07F9/65512 , C07G3/00 , C12Q1/37 , G01N33/582 , Y02P20/55 , Y10S435/81
摘要： A new class of stable dioxetanes bears a polycyclic stabilizing group and aryloxy moiety, the oxygen atom of which is provided with a protective group which can be removed by an enzymatic or chemical trigger admixed with the dioxetane. The polycyclic stabilizing group is preferably spiroadamantane. The group further bears an alkoxy, aryloxy, aralkyloxy or cycloalkyloxymoiety which is partially or completely substituted with halogens, particularly fluorine and chlorine. Proper selection of electron active groups on the stabilizing moiety, the aryl group and the OR group yields enhanced enzyme kinetics, superior light intensity and excellent detection sensitivity in various assays.
摘要翻译：一类稳定的二氧杂环丁烷具有多环稳定基团和芳氧基部分，其氧原子具有可以通过与二氧杂环丁烷混合的酶或化学触发剂除去的保护基团。多环稳定基团优选为四金刚烷。该基团还具有部分或完全被卤素，特别是氟和氯取代的烷氧基，芳氧基，芳烷氧基或环烷氧基。稳定部分，芳基和OR基上的电子活性基团的适当选择在各种测定中产生增强的酶动力学，优异的光强度和优异的检测灵敏度。

6. 发明授权

US5582980A Chemiluminescent 1,2-dioxetanes 失效
标题翻译：化学发光的1,2-二氧杂环丁烷
公开(公告)号：US5582980A
公开(公告)日：1996-12-10
申请号：US231673
申请日：1994-04-25
申请人： Irena Bronstein , Brooks Edwards , Alison Sparks
发明人： Irena Bronstein , Brooks Edwards , Alison Sparks
IPC分类号： G01N33/532 , A43B3/00 , C07C43/178 , C07C43/196 , C07C43/215 , C07C43/225 , C07C43/23 , C07C43/315 , C07C45/67 , C07C47/565 , C07C47/575 , C07C65/03 , C07C65/21 , C07C69/00 , C07C69/017 , C07C69/24 , C07C69/78 , C07C69/84 , C07C69/92 , C07C205/06 , C07C205/37 , C07C205/44 , C07C217/84 , C07C233/18 , C07C233/75 , C07C271/28 , C07C271/58 , C07C309/75 , C07C311/04 , C07C311/08 , C07C311/16 , C07D321/00 , C07F7/08 , C07F7/18 , C07F9/12 , C07F9/40 , C07F9/655 , C07F9/6574 , C07G3/00 , C07H15/203 , C07H15/26 , C12Q1/34 , C12Q1/37 , C12Q1/42 , C12Q1/68 , G01N21/76 , G01N21/78 , G01N33/52 , G01N33/535 , G01N33/58 , C12Q1/00 , C07H15/24 , G01N33/53
CPC分类号： G01N33/582 , A43B1/0036 , A43B1/0072 , A43B3/0031 , C07C205/37 , C07C205/44 , C07C217/84 , C07C233/18 , C07C271/28 , C07C271/58 , C07C43/1788 , C07C43/196 , C07C43/215 , C07C43/225 , C07C43/23 , C07C43/315 , C07C45/673 , C07C47/565 , C07C47/575 , C07C65/03 , C07C65/21 , C07D321/00 , C07F9/12 , C07F9/4056 , C07F9/65512 , C07F9/65742 , C07G3/00 , C07H15/203 , C07H15/26 , C12Q1/34 , C12Q1/37 , C12Q1/42 , G01N21/76 , G01N33/581 , C07C2103/74 , C12Q2334/00 , Y10S435/81 , Y10S435/975
摘要： Spiroadamantyl dioxetanes bearing an alkoxy substituent, and a phenyl substituted on the dioxetane ring can be activated to chemiluminesce if the aromatic substituent bears a meta-substituted moiety designated OX, wherein the X is cleaved by an enzyme with which the dioxetane is permitted to come in contact with. The T.sub.1/2 kinetics of the chemiluminescent reaction, as well as the signal intensity and/or quantum yield of the chemiluminescent reaction, can be altered by addition of a chlorine substituent at position 4 on the phenyl ring. Signal strength can further be enhanced by recognized chemiluminescent enhancers.
摘要翻译：如果芳香族取代基具有指定为OX的间位取代的部分，则可以将带有烷氧基取代基的双金刚烷基二氧杂环丁烷和在二氧杂环丁烷环上取代的苯基活化成化学发光，其中X被允许进行二氧杂环丁烷的酶切割接触。化学发光反应的T + E，fra 1/2 + EE动力学以及化学发光反应的信号强度和/或量子产率可以通过在苯环上的第4位加入氯取代基来改变。信号强度可以通过认可的化学发光增强剂进一步增强。

7. 发明授权

US5336596A Membrane for chemiluminescent blotting applications 失效
标题翻译：用于化学发光印迹应用的膜
公开(公告)号：US5336596A
公开(公告)日：1994-08-09
申请号：US811620
申请日：1991-12-23
申请人： Irena Bronstein , Brooks Edwards , John Voyta
发明人： Irena Bronstein , Brooks Edwards , John Voyta
IPC分类号： G01N21/78 , B32B27/30 , C09D125/00 , C09D125/18 , G01N33/545 , G01N33/58 , C12B1/68 , B32B27/00
CPC分类号： G01N33/582 , G01N33/545 , Y10T428/31536 , Y10T428/31743 , Y10T428/31884
摘要： A new and improved polymeric membrane for use in biological assays is provided. A blotting assay employing 1,2-dioxetanes as a source of chemiluminescence employs, as an improved membrane, a polymer comprised of at least one monomer of the formula: ##STR1## The membranes reduce background signal, improve sensitivity and reliability.
摘要翻译：提供了用于生物测定的新的和改进的聚合物膜。使用1,2-二氧杂环丁烷作为化学发光源的印迹测定使用由至少一种下式的单体组成的聚合物作为改进的膜：提高了灵敏度和可靠性。

8. 发明授权

US06852548B2 Benzothiazole dioxetanes 有权
标题翻译：苯并噻唑二氧杂环丁烷
公开(公告)号：US06852548B2
公开(公告)日：2005-02-08
申请号：US09945661
申请日：2001-09-05
申请人： Brooks Edwards , Irena Bronstein
发明人： Brooks Edwards , Irena Bronstein
IPC分类号： G01N21/76 , C07D277/62 , C07D417/04 , C07D493/04 , C07F9/655 , C07F9/6558 , C12Q1/42 , G01N21/78 , G01N33/58 , G01N33/533 , G01N33/532
CPC分类号： C07D277/62 , C07D417/04 , C07D493/04 , C07F9/65512 , C07F9/65586 , G01N33/582 , Y10S530/807
摘要： Chemiluminescent 1,2-dioxetane compounds capable of producing light energy when decomposed, substantially stable at room temperature, represented by the formulas I or II: wherein T is:
摘要翻译：化学发光的1,2-二氧杂环丁烷化合物当分解时能够产生光能，在室温下基本稳定，由式I或II表示：其中T为：

9. 发明授权

US6140495A Chemiluminescent 1,2-dioxetanes 失效
标题翻译：化学发光的1,2-二氧杂环丁烷
公开(公告)号：US6140495A
公开(公告)日：2000-10-31
申请号：US296539
申请日：1999-04-22
申请人： Irena Bronstein , Brooks Edwards , Alison Sparks
发明人： Irena Bronstein , Brooks Edwards , Alison Sparks
IPC分类号： C07D321/00 , C07D327/06 , C07F9/02 , C07F9/06 , C07F9/28 , C07H19/04
CPC分类号： C07D321/00
摘要： Spiroadamantyl dioxetanes bearing an alkoxy substituent, and an aromatic substituent of phenyl or naphthyl on the dioxetane ring can be activated to chemiluminesce if the aromatic substituent bears a moiety designated OX, wherein the X is cleaved by an enzyme with which the dioxetane is permitted to come in contact with. The T.sub.1/2 kinetics of the chemiluminescent reaction, as well as the signal intensity, or quantum yield of the chemiluminescent reaction, can be altered by selection of an electron-withdrawing or an electron-donating group Z, at positions on the aromatic substituent other than those adjacent the point of attachment to the dioxetane. Signal strength can further be enhanced by recognized chemiluminescent enhancers.
摘要翻译：具有烷氧基取代基的双金刚烷基二氧杂环丁烷和二氧杂环丁烷环上苯基或萘基的芳族取代基可以被活化成化学发光，如果芳族取代基具有指定为OX的部分，其中X被允许二氧杂环丁烷的酶切割在与接触。化学发光反应的T + E，1/2 + EE动力学以及化学发光反应的信号强度或量子产率可以通过选择吸电子基团或给电子基团Z来改变，在芳族取代基上除了与二氧杂环丁烷的连接点相邻的位置之外的位置。信号强度可以通过认可的化学发光增强剂进一步增强。

10. 发明授权

US5843681A Dioxetane compounds for the chemiluminescent detection of proteases, methods of use and kits therefore 失效
标题翻译：因此，用于化学发光检测蛋白酶的二氧杂环丁烷化合物，使用方法和试剂盒
公开(公告)号：US5843681A
公开(公告)日：1998-12-01
申请号：US728990
申请日：1996-10-11
申请人： Irena Bronstein , Brooks Edwards , Christopher Martin , Alison Sparks , John C. Voyta
发明人： Irena Bronstein , Brooks Edwards , Christopher Martin , Alison Sparks , John C. Voyta
IPC分类号： G01N33/573 , C07D321/00 , C07K5/072 , C07K5/08 , C07K5/09 , C07K5/10 , C12Q1/37 , G01N33/58
CPC分类号： C07K5/06095 , C07D321/00 , C07K5/0802 , C07K5/0817 , C07K5/1002 , C12Q1/37 , G01N33/582 , Y10S530/807
摘要： 1, 2-dioxetane compounds bearing a proteolytic enzyme specific amino acid or peptide are provided, which amino acid or peptide can be removed by action of the corresponding protease. When the amino acid or peptide is removed, the 1,2-dioxetane decomposes with chemiluminescence, the generation of light providing a rapid, ultra-sensitive and convenient means for detecting the presence of the protease in the sample being inspected. The amount of light generated, or degree of chemiluminescence, can be correlated with the amount of protease present. Immunoassays, as well as DNA hybridization and DNA probe assays are provided.
摘要翻译：提供了带有蛋白水解酶特异性氨基酸或肽的1,2-二氧杂环丁烷化合物，该氨基酸或肽可以通过相应的蛋白酶的作用除去。当去除氨基酸或肽时，1,2-二氧杂环丁烷以化学发光分解，产生光，提供快速，超灵敏和方便的手段，用于检测待检样品中蛋白酶的存在。产生的光量或化学发光度可以与存在的蛋白酶的量相关。提供免疫测定，以及DNA杂交和DNA探针测定。

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