公开(公告)号：US20040248227A1

公开(公告)日：2004-12-09

申请号：US10479399

申请日：2004-06-15

发明人： Kristian Jansson ,  Vuokko Jansson

IPC分类号： C12Q001/48

CPC分类号： C12Q1/48 ,  C12Q1/26 ,  C12Q1/28

摘要： A method for determining inorganic pyrophosphate in a sample, which method comprises contacting the sample with an aqueous reagent comprising xanthosine 5null-monophosphate (XMP) or preferrably inosine 5null-monophosphate (IM), xanthosine phosphoribosyltransferase or preferrably hypoxanthine phosphoribosyltransferase, xanthine oxidase, a divalent cation which is preferrably Mg2null, and a buffering agent which is preferably tris(hydroxymethyl)aminomethane (Tris); and determining production of hydrogen peroxide as a measure or inorganic pyrophosphate in the sample. Preferrably, the reagent further comprises uricase.

公开(公告)号：US20040241780A1

公开(公告)日：2004-12-02

申请号：US10878276

申请日：2004-06-28

发明人： J. Bryan Jones ,  Erika Plettner

IPC分类号： C12Q001/48 ,  C12Q001/34 ,  C12Q001/37

CPC分类号： C12Q1/44 ,  C12Q1/34

摘要： The present invention relates to a method for screening chemically modified mutant enzymes for amidase and/or esterase activity. This method includes providing a chemically modified mutant enzyme with one or more amino acid residues from an enzyme being replaced by cysteine residues, where at least some of the cysteine residues are modified by replacing thiol hydrogen in the cysteine residues with a thiol side chain, contacting the chemically modified mutant enzyme with a substrate for an amidase and/or a substrate for an esterase, and determining whether the chemically modified mutant enzyme exhibits amidase and/or esterase activity. The present invention also relates to chemically modified mutant enzymes and a method of producing them where one or more amino acid residues from an enzyme are replaced by cysteine residues, and the cysteine residues are modified by replacing at least some of the thiol hydrogen in the cysteine residue with a thiol side chain to form the chemically modified mutant enzyme. The thiol side chain is selected from the group consisting of nullSCH2(p-CH3nullC6H4), nullSCH2(p-OCH3nullC6H4), nullSCH2(p-CF3nullC6H4), and nullSCH2(2,4-diNO2nullC6H3).

摘要翻译： 本发明涉及用于筛选化学修饰的突变酶用于酰胺酶和/或酯酶活性的方法。 该方法包括提供化学修饰的突变酶，其具有由半胱氨酸残基取代的酶中的一个或多个氨基酸残基，其中至少一些半胱氨酸残基通过用巯基侧链取代半胱氨酸残基中的硫醇氢而被修饰， 化学修饰的突变酶，其具有用于酰胺酶和/或酯酶底物的底物，以及确定化学修饰的突变酶是否显示酰胺酶和/或酯酶活性。 本发明还涉及化学修饰的突变酶及其制备方法，其中来自酶的一个或多个氨基酸残基被半胱氨酸残基取代，半胱氨酸残基被替换半胱氨酸中的至少一些巯基氢 残基用硫醇侧链形成化学修饰的突变酶。 硫醇侧链选自-SCH 2（p-CH 3 -C 6 H 4），-SCH 2（p-OCH 3 -C 6 H 4），-SCH 2（对CF 3 -C 6 H 4）和-SCH 2（2,4-二硝基 -C 6 H 3）。

公开(公告)号：US20040180392A1

公开(公告)日：2004-09-16

申请号：US10490462

申请日：2004-03-23

发明人： Thomayant Prueksaritanont

IPC分类号： C12Q001/48

CPC分类号： C12Q1/48 ,  A61K31/19 ,  A61K31/366 ,  A61K31/40 ,  G01N2333/90245 ,  G01N2333/91245 ,  G01N2500/04 ,  A61K2300/00

摘要： A method for screening statins in their open acid form to determine the susceptibility of each tested statin to metabolic glucuronidation is provided. Also provided is a method for determining if a non-statin pharmaceutical drug co-administered with a statin that is susceptible to metabolic glucuronidation in its open acid form, will inhibit the glucuronidation of the statin and thereby increase the risk of an adverse drug interaction.

摘要翻译： 提供了以开放酸形式筛选他汀类药物以确定每种被测他汀类药物对代谢葡萄糖醛酸化的敏感性的方法。 还提供了一种用于确定与其开放酸形式易于代谢葡糖醛酸化的他汀类药物共同施用的非他汀类药物是否将抑制他汀类药物葡糖醛酸化，从而增加不良药物相互作用的风险的方法。

公开(公告)号：US20040110232A1

公开(公告)日：2004-06-10

申请号：US10626173

申请日：2003-07-24

申请人： Millennium Pharmaceuticals, Inc.

发明人： Jeyaseelan Raju

IPC分类号： G01N033/53 ,  C12Q001/48

CPC分类号： C12N9/1205 ,  C07K2319/00 ,  C12Q1/485 ,  G01N2500/04

摘要： The invention provides isolated nucleic acids molecules, designated CARK nucleic acid molecules. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing CARK nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a CARK gene has been introduced or disrupted. The invention still further provides isolated CARK proteins, fusion proteins, antigenic peptides and anti-CARK antibodies. Diagnostic methods utilizing compositions of the invention are also provided.

摘要翻译： 本发明提供分离的核酸分子，命名为CARK核酸分子。 本发明还提供反义核酸分子，含有CARK核酸分子的重组表达载体，其中引入了表达载体的宿主细胞，以及其中引入或破坏CARK基因的非人类转基因动物。 本发明还进一步提供了分离的CARK蛋白，融合蛋白，抗原肽和抗CARK抗体。 还提供了利用本发明组合物的诊断方法。

公开(公告)号：US20040106637A1

公开(公告)日：2004-06-03

申请号：US10639263

申请日：2003-08-12

申请人： The Regents of the University of Michigan

发明人： Kun-Liang Guan

IPC分类号： A61K031/4745 ,  G01N033/53 ,  G01N033/537 ,  G01N033/543 ,  C12Q001/48

CPC分类号： G01N33/5041 ,  C12Q1/485

摘要： The present invention relates to compositions and methods for identifying abnormalities in TSC signaling pathways. In particular, the present invention relates to methods of diagnosing and treating disorders such as tuberous sclerosis, which are caused by mutations in the TSC genes. The present invention further relates to methods and compositions for treating cancers mediated by TSC signaling disorders.

摘要翻译： 本发明涉及鉴定TSC信号通路异常的组合物和方法。 特别地，本发明涉及诊断和治疗由TSC基因突变引起的结节性硬化症等疾病的方法。 本发明还涉及用于治疗由TSC信号传导疾病介导的癌症的方法和组合物。

公开(公告)号：US20030180797A1

公开(公告)日：2003-09-25

申请号：US10103535

申请日：2002-03-20

发明人： Lin Yu ,  Qing Dong ,  Fabrice Pierre

IPC分类号： G01N033/53 ,  C12Q001/48 ,  G01N033/543

CPC分类号： G01N33/566 ,  C12Q1/00

摘要： The invention provides a method of identifying a population of bi-ligands to receptors in a receptor family. The method can include the steps of generating a first population of molecules comprising a specificity ligand having binding activity for a receptor in a receptor family, the specificity ligand attached to a first plurality of chemical moieties at a position on the specificity ligand to direct the specificity ligand to a specificity site and the chemical moieties to a conserved site of the receptor; screening the population of molecules for binding to the receptor; and identifying a bi-ligand having increased binding activity for the receptor relative to the specificity ligand alone, thereby identifying a common ligand having binding activity for the receptor. The method can further include the steps of generating a second population of molecules comprising the common ligand attached to a second plurality of chemical moieties.

摘要翻译： 本发明提供了鉴定受体家族中受体的双配体群体的方法。 该方法可以包括以下步骤：产生包含对受体家族中的受体具有结合活性的特异性配体的第一群体分子，所述特异性配体连接于特异性配体上位置上的第一多个化学部分以引导特异性 特异性位点的配体和化学部分到受体的保守位点; 筛选与受体结合的分子群; 并鉴定相对于单独的特异性配体具有增加的受体结合活性的双配位体，从而鉴定具有受体结合活性的共同配体。 该方法还可以包括产生包含连接到第二多个化学部分的共同配体的第二群分子的步骤。

公开(公告)号：US20030170767A1

公开(公告)日：2003-09-11

申请号：US10293580

申请日：2002-11-12

申请人： Aurora Biosciences Corporation

发明人： Andrew B. Cubitt

IPC分类号： C12Q001/48 ,  C12Q001/37 ,  C07H021/04 ,  C12P021/02 ,  C12N005/06 ,  C07K014/435

CPC分类号： C07K14/43595

摘要： The present invention includes a fluorescent compound that can detect an activity. such as an enzymatic activity, and exhibits quenching. The fluorescent compound can include a fluorescent protein, such as an Aequorea-related green fluorescent protein. The fluorescent compound can include a substrate site for an enzymatic activity such as a kinase activity, a phosphatase activity, a protease activity, and a glycosylase activity The fluorescent compound of the present invention can be used to detect such enzymatic activities in samples, such as biological samples, including cells. The present invention also includes nucleic acids that encode the fluorescent compounds of the present inventions, and cells that include such nucleic acids or fluorescent compounds.

摘要翻译： 本发明包括能够检测活性的荧光化合物。 例如酶活性，并显示淬灭。 荧光化合物可以包括荧光蛋白，例如与水母相关的绿色荧光蛋白。 荧光化合物可以包括酶活性的底物位点，例如激酶活性，磷酸酶活性，蛋白酶活性和糖基化酶活性。本发明的荧光化合物可用于检测样品中的这种酶活性，例如 生物样品，包括细胞。 本发明还包括编码本发明的荧光化合物的核酸和包括这种核酸或荧光化合物的细胞。

公开(公告)号：US20030170737A1

公开(公告)日：2003-09-11

申请号：US10093945

申请日：2002-03-09

发明人： Michael H. Cardone ,  Michael Yaffe

IPC分类号： G01N033/53 ,  G01N033/567 ,  C12Q001/48

CPC分类号： C12Q1/25 ,  C12Q1/485 ,  G01N2500/00

摘要： Cell-based screening methods for determining kinase activity are provided. The methods utilize existing cellular pathways that are regulated by kinases. In one embodiment, various components of a ubiquitin-mediated degradation pathway are modified to create an assay that can be used to screen for a molecule that modulates the activity of a kinase of interest that otherwise does not regulate the degradation pathway. In another embodiment, various components of a protein translocation pathway are modified to screen for a molecule that modulates the activity of a kinase of interest that otherwise does not regulate the translocation pathway.

公开(公告)号：US20030113782A1

公开(公告)日：2003-06-19

申请号：US10303683

申请日：2002-11-25

发明人： Felix D. Karim ,  Linda Nolan Keyes ,  Gregory D. Plowman

IPC分类号： C12Q001/68 ,  G01N033/53 ,  G01N033/567 ,  C12Q001/48

CPC分类号： C12Q1/485 ,  C12Q1/6886 ,  C12Q2600/158 ,  G01N33/573 ,  G01N33/57407 ,  G01N33/57484 ,  G01N2333/91205 ,  G01N2500/02

摘要： Human MAP4K genes are identified as modulators of branching morphogenesis, and thus are therapeutic targets for disorders associated with defective branching morphogenesis function. Methods for identifying modulators of branching morphogenesis, comprising screening for agents that modulate the activity of MAP4K are provided.

摘要翻译： 人MAP4K基因被鉴定为分支形态发生的调节剂，因此是与缺陷支配形态发生功能相关的病症的治疗靶点。 提供用于鉴定分支形态发生调节剂的方法，包括筛选调节MAP4K活性的试剂。

公开(公告)号：US20030113711A1

公开(公告)日：2003-06-19

申请号：US10155481

申请日：2002-05-24

发明人： Robert Kevin Blackburn ,  Harold Neal Bramson ,  Mary Benbow Moyer ,  James Darren Stuart

IPC分类号： C12Q001/70 ,  G01N033/53 ,  C12Q001/48

CPC分类号： C07K7/08 ,  C12Q1/485 ,  G01N2500/00

摘要： A method of isolating and identifying peptide substrates for a protein kinase is disclosed. The method involves a combination of size exclusion and gallium-based metal affinity chromatography. The method includes the steps of incubating a protein kinase with a peptide library in the presence of kinase reaction components, the library comprising library members; separating library members from the kinase reaction components using size exclusion chromatography to give a pool of phosphopeptides and unphosphorylated peptides; contacting the pool with immobilized gallium ions to form chelated phosphopeptides; eluting chelated phosphopeptides away from the gallium ions to give eluted phosphopeptides; sequencing the eluted phosphopeptides, whereby a preferred amino acid sequence of a preferred peptide substrate for a protein kinase is elucidated. Also disclosed is a method of identifying a compound that modulates the protein kinase catalyzed phosphorylation of a peptide substrate and a method of designing protein kinase substrates.

摘要翻译： 公开了分离和鉴定蛋白激酶的肽底物的方法。 该方法涉及尺寸排阻和镓基金属亲和层析的组合。 该方法包括在激酶反应组分存在下将蛋白激酶与肽文库一起孵育的步骤，该文库包含文库成员; 使用大小排阻色谱法将文库成员与激酶反应组分分离，得到一组磷酸肽和未磷酸化的肽; 使池与固定的镓离子接触以形成螯合的磷酸肽; 从螯合磷酸肽离开镓离子得到洗脱的磷酸肽; 对洗脱的磷酸肽进行测序，从而阐明用于蛋白激酶的优选肽底物的优选氨基酸序列。 还公开了鉴定调节蛋白激酶催化的肽底物磷酸化的化合物的方法和设计蛋白激酶底物的方法。