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1. 发明公开

US20240271205A1 NUCLEOTIDE CLEAVABLE LINKERS AND USES THEREOF 审中-公开
公开(公告)号：US20240271205A1
公开(公告)日：2024-08-15
申请号：US18598995
申请日：2024-03-07
申请人： Singular Genomics Systems, Inc.
发明人： Ronald GRAHAM , Olga ADELFINSKAYA , Megha CILA , Rodrigo RODRIGUEZ
IPC分类号： C12Q1/6869 , C07F9/655 , C07H19/06 , C07H19/10 , C07H19/14 , C07H19/16 , C07H19/20 , C12N9/12 , C12Q1/6806
CPC分类号： C12Q1/6869 , C07F9/65515 , C07H19/06 , C07H19/10 , C07H19/14 , C07H19/16 , C07H19/20 , C12N9/1241 , C12Q1/6806 , C12Q2334/40 , C12Q2521/101 , C12Q2525/101 , C12Q2535/00
摘要： Disclosed herein, inter alia, are compounds, compositions, and methods of use thereof for sequencing a nucleic acid.

2. 发明申请

US20190233871A1 SPECIFIC SUBSTRATE OF AN ALDH ISOENZYME 审中-公开
公开(公告)号：US20190233871A1
公开(公告)日：2019-08-01
申请号：US16320071
申请日：2017-07-27
申请人： ADVANCED BIODESIGN , Centre national de la recherche scientifique , Université Claude Bernard Lyon 1
发明人： Ismail CEYLAN , Guillaume MARTIN , Gérard QUASH , Milleidys PEREZ-ALEA , Guy FOURNET
IPC分类号： C12Q1/00 , C12Q1/32
CPC分类号： C12Q1/007 , C12Q1/32 , C12Q2334/20 , C12Q2334/40
摘要： The invention relates to a specific substrate on an ALDH isoenzyme, to a composition comprising at least one such substrate, to a diagnostic marker comprising such a substrate, and to the uses thereof and associated methods.

3. 发明授权

US5362628A Fluorescent haloalkyl derivatives of reporter molecules well retained in cells 失效
标题翻译：报道分子的荧光卤代烷基衍生物保留在细胞中
公开(公告)号：US5362628A
公开(公告)日：1994-11-08
申请号：US26633
申请日：1993-03-05
申请人： Richard P. Haugland , Yu-Zhong Zhang , Ram Sabnis , Nels A. Olson , John J. Naleway , Rosaria P. Haugland
发明人： Richard P. Haugland , Yu-Zhong Zhang , Ram Sabnis , Nels A. Olson , John J. Naleway , Rosaria P. Haugland
IPC分类号： C12Q1/04 , C12Q1/34 , G01N33/535 , C12Q1/00 , A61K37/02 , C07H15/24 , G01N33/40
CPC分类号： C12Q1/04 , C12Q1/34 , G01N33/535 , C12Q2334/00 , C12Q2334/20 , C12Q2334/40 , C12Q2337/20 , G01N2333/924 , Y10S530/802
摘要： The subject invention provides a method for analyzing the metabolic activity in cells by improving the retention of a detectable reporter molecule only in intact cells where a particular enzyme is present. In particular, improved retention results from a two part process involving conjugation of haloalkyl-substituted derivatives of a reporter molecule with intracellular cysteine-containing peptides while unblocking the reporter molecule. The method for analyzing metabolic activity of cells involves the use of a substrate having the formXR-REPORTER-BLOCKwherein -BLOCK is a group selected to be removable by action of a specific analyte, to give REPORTER spectral properties different from those of the substrate,-REPORTER- is a molecule that, when no longer bound to BLOCK by a BLOCK-REPORTER bond, has spectral properities different from those of the substrate, andXR-- is a haloalkyl moiety that can covalently react with an intracellular thiol (Z--S--H) to form a thioether conjugate (Z--S--R--).After the substrate enters the cells, the analyte removes BLOCK to make REPORTER detectable by the change in spectral properties, and the haloalkyl XR reacts with the intracellular thiol to form the thioether conjugate inside the cells, which is well-retained in the cells.
摘要翻译：本发明提供了通过仅在存在特定酶的完整细胞中改善可检测报道分子的保留来分析细胞中的代谢活性的方法。特别地，涉及将报道分子的卤代烷基取代的衍生物与含细胞内半胱氨酸的肽结合的两部分方法的改进的保留结果，同时解除报道分子的阻断。用于分析细胞代谢活性的方法涉及使用具有XR-REPORTER-BLOCK形式的底物，其中-BLOCK是通过特定分析物的作用被选择为可去除的基团，以产生与底物的不同的REPORTER光谱性质 -REPORTER-是一个分子，当不再通过BLOCK-REPORTER键与BLOCK结合时，具有与底物不同的光谱性质，XR-是可以与胞内硫醇（ZSH）共价反应的卤代烷基部分，以形成硫醚缀合物（ZSR-）。在底物进入细胞后，分析物除去BLOCK以通过光谱性质的变化使REPORTER可检测到，并且卤代烷基XR与细胞内硫醇反应以在细胞内形成硫醚缀合物，其在细胞中良好保留。

4. 发明授权

US4985414A 1-naphtholphthalein monophosphates and diagnostic reagents containing them 失效
标题翻译： 1-萘酚酞和含有它们的诊断试剂
公开(公告)号：US4985414A
公开(公告)日：1991-01-15
申请号：US273403
申请日：1988-11-18
申请人： Werner Guethlein , Hartmut Merdes
发明人： Werner Guethlein , Hartmut Merdes
IPC分类号： C07F9/09 , C07F9/12 , C07F9/655 , C12Q1/42 , G01N33/50
CPC分类号： C12Q1/42 , C07F9/65517 , C12Q2334/40
摘要： New 1-naphtholphthalein monophosphates of the formula ##STR1## wherein each of R.sup.1 and R.sup.2 is hydrogen or halogen, and each of M.sup.1 and M.sup.2 is a proton or an alkali metal, alkaline earth metal, ammonium, dicyclohexylammonium, tetraalkylammonium or alkanolammonium cation, and the tautomeric transformation products thereof, are useful as substrates for detection and photometric determination of alkaline phosphotase.
摘要翻译：式中，R1，R2分别为氢或卤素，M1和M2各自为质子或碱金属，碱土金属，铵，二环己基铵，四烷基铵或链烷醇铵阳离子的新型1-萘酚酞单磷酸盐，其互变异构转化产物可用作碱性磷酸酶的检测和光度测定的底物。

5. 再颁专利

USRE38723E1 Haloalkyl derivatives of reporter molecules used to analyze metabolic activity in cells 失效
标题翻译：用于分析细胞代谢活性的报道分子的卤代烷基衍生物
公开(公告)号：USRE38723E1
公开(公告)日：2005-04-12
申请号：US08910090
申请日：1997-08-12
申请人： Fei Mao , Ram Sabnis , John Naleway , Nels Olson , Richard P. Haugland
发明人： Fei Mao , Ram Sabnis , John Naleway , Nels Olson , Richard P. Haugland
IPC分类号： C12Q1/04 , C12Q1/34 , G01N33/535 , C07H17/00 , C07D309/00
CPC分类号： G01N33/535 , C12Q1/04 , C12Q1/34 , C12Q2334/00 , C12Q2334/20 , C12Q2334/40 , C12Q2337/20 , G01N2333/924
摘要： The subject invention provides substrates useful for analyzing the metabolic activity in cells by improving the retention of a detectable reporter molecule only in intact cells where a particular enzyme is present. In particular, improved retention results from a two part process involving conjugation of haloalkyl-substituted derivatives of a reporter molecule with intracellular cysteine-containing peptides while unblocking the reporter molecule. The substrates have the form XR-SPACER-REPORTER-BLOCK wherein -BLOCK is a group selected to be removable by action of a specific analyte, to give REPORTER spectral properties different from those of the substrate, -REPORTER- is a molecule that, when no longer bound to BLOCK by a BLOCK-REPORTER bond, has spectral properties different from those of the substrate, -SPACER- is a covalent linkage, and XR- is a haloalkyl moiety that can covalently react with an intracellular thiol (Z-S-H) to form a thioether conjugate (Z-S-R). After the substrate enters the cells, the analyte removes BLOCK to make REPORTER detectable by the change in spectral properties, and the haloalkyl XR reacts with the intracellular thiol to form the thioether conjugate inside the cells, which is well-retained in the cells.

6. 发明授权

US5155026A Method for determination of nagase and reagent therefor 失效
标题翻译：用于确定NAGASE及其试剂的方法
公开(公告)号：US5155026A
公开(公告)日：1992-10-13
申请号：US723652
申请日：1991-06-26
申请人： Akira Noto , Kunihiro Nakajima , Kazuyuki Sasakura , Tsutomu Sugasawa
发明人： Akira Noto , Kunihiro Nakajima , Kazuyuki Sasakura , Tsutomu Sugasawa
IPC分类号： G01N33/50 , C12Q1/34 , C12Q1/54
CPC分类号： C12Q1/34 , C12Q1/54 , C12Q2334/40 , G01N2333/924 , Y10S435/81
摘要： Highly sensitive reagent for colorimetrically determining N-acetyl-.beta.-D-glucosaminidase (NAGase) activity by the continuous method, comprising sodio-3,3'-dichlorophenolsulfonphthaleinyl N-acetyl-.beta.-D-glucosaminide and a buffer, with which renal dysfunction can be diagnosed precisely, quickly, and easily.

7. 发明授权

US4045290A Diagnostic method and compounds for use therewith 失效
标题翻译：诊断方法和与其一起使用的化合物
公开(公告)号：US4045290A
公开(公告)日：1977-08-30
申请号：US659002
申请日：1976-02-18
申请人： George F. Bulbenko , Joseph Eliot Woodbridge
发明人： George F. Bulbenko , Joseph Eliot Woodbridge
IPC分类号： C07F9/09 , C07F9/655 , C07F9/6553 , C12Q1/42 , G07F3/02 , C09K15/26
CPC分类号： C12Q1/42 , C07F9/65517 , C12Q2334/40
摘要： An assay for phosphatase enzymes in body fluids comprising contacting a sample of such body fluid with the substrate, Thymol Blue Monophosphate, which is chromogenic at the pH of the reaction mixture and determining activity of the enzyme by measuring the rate of formation of the Thymol Blue dye.
摘要翻译：一种用于体液中的磷酸酶的测定法，其包括使这种体液的样品与底物，百里酚蓝单磷酸酯接触，所述底物是在反应混合物的pH下显色，并通过测定百里酚蓝的形成速率来测定酶的活性染料。

8. 发明授权

US3975405A Monophosphate salt of o-cresolphthalein 失效
标题翻译：邻甲酚酞的单磷酸盐
公开(公告)号：US3975405A
公开(公告)日：1976-08-17
申请号：US493775
申请日：1974-08-01
申请人： Thomas E. Hamill
发明人： Thomas E. Hamill
IPC分类号： C07F9/655 , C12Q1/42 , C07D307/94 , C12K1/04
CPC分类号： C12Q1/42 , C07F9/65517 , C12Q2334/40
摘要： O-cresolphthalein monophosphoric acid and salts thereof useful as substrates for alkaline phosphatase determinations are produced by reacting cresolphthalein with dibenzyl phosphite in the presence of carbon tetrachloride and an organic amine, hydrogenating the reaction product, recovering o-cresolphthalein monophosphoric acid from the hydrogenation product, and reacting the acid with bases to produce desired salts.
摘要翻译：用作碱性磷酸酶测定底物的O-甲酚酞单磷酸及其盐是通过在四氯化碳和有机胺存在下使甲酚酞与亚磷酸二苄酯反应，氢化反应产物，从氢化产物中回收邻甲酚酞一磷酸，并使酸与碱反应以产生所需的盐。

9. 发明授权

US11970735B2 Nucleotide cleavable linkers and uses thereof 有权
公开(公告)号：US11970735B2
公开(公告)日：2024-04-30
申请号：US17417332
申请日：2020-01-07
申请人： Singular Genomics Systems, Inc.
发明人： Ronald Graham , Olga Adelfinskaya , Megha Cila , Rodrigo Rodriguez
IPC分类号： C12Q1/6869 , C07F9/655 , C07H19/06 , C07H19/10 , C07H19/14 , C07H19/16 , C07H19/20 , C12N9/12 , C12Q1/6806
CPC分类号： C12Q1/6869 , C07F9/65515 , C07H19/06 , C07H19/10 , C07H19/14 , C07H19/16 , C07H19/20 , C12N9/1241 , C12Q1/6806 , C12Q2334/40 , C12Q2521/101 , C12Q2525/101 , C12Q2535/00
摘要： Disclosed herein, inter alia, are compounds, compositions, and methods of use thereof for sequencing a nucleic acid.

10. 发明授权

US5776720A Assay reagent 失效
标题翻译：分析试剂
公开(公告)号：US5776720A
公开(公告)日：1998-07-07
申请号：US443776
申请日：1995-05-18
申请人： Gerald E. Jaffe , Frank J. Lucas , James H. Carter
发明人： Gerald E. Jaffe , Frank J. Lucas , James H. Carter
IPC分类号： C12Q1/02 , C12Q1/34 , G01N33/574 , C12Q1/00
CPC分类号： C12Q1/34 , C12Q1/02 , G01N33/574 , C12Q2334/40 , C12Q2337/40
摘要： An assay compound or a salt thereof for assaying the activity of an enzyme inside a metabolically active whole cell is disclosed. The assay compound includes a leaving group and an indicator group. The leaving group is selected from the group comprising amino acids, peptides, saccharides, sulfates, phosphates, esters, phosphate esters, nucleotides, polynucleotides, nucleic acids, pyrimidines, purines, nucleosides, lipids and mixtures thereof. The indicator group is selected from compounds which have a first state when joined to the leaving group, and a second state when the leaving group is cleaved from the indicator group by the enzyme. Preferably, the indicator compounds are rhodamine 110, rhodol, and fluorescein and analogs of these compounds. A method of synthesizing the compound as well as methods of using these compounds to measure enzyme activity are also disclosed.
摘要翻译：公开了一种用于测定代谢活性整个细胞内的酶的活性的测定化合物或其盐。测定化合物包括离去基团和指示剂组。离去基团选自包括氨基酸，肽，糖，硫酸盐，磷酸盐，酯，磷酸酯，核苷酸，多核苷酸，核酸，嘧啶，嘌呤，核苷，脂质及其混合物的组。指示基团选自与离去基团连接时具有第一状态的化合物，当离去基团被酶从指示剂基团切割时的第二种状态。优选地，指示剂化合物是这些化合物的罗丹明110，rhodol和荧光素以及类似物。还公开了合成化合物的方法以及使用这些化合物测定酶活性的方法。

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