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1.发明申请公开(公告)号：US20090136477A1
公开(公告)日：2009-05-28
申请号：US12005949
申请日：2007-12-28
CPC分类号： C12N9/6467 , C07K2319/50 , C12N9/6475 , C12Q1/37 , G01N2500/00
摘要： Disclosed herein are methods for generating proteases with altered specificity for the target molecules they cleave. The invention further discloses methods of using these proteases to treat diseases in which the target proteins are involved with. Cleaving certain target proteins at certain substrate sequences with a protease is a method for treating these pathologies.
摘要翻译： 本文公开了用于产生对其切割的靶分子具有特异性改变的蛋白酶的方法。 本发明进一步公开了使用这些蛋白酶治疗涉及靶蛋白的疾病的方法。 用蛋白酶在某些底物序列上切割某些靶蛋白是治疗这些病症的方法。
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公开(公告)号：US07227009B2
公开(公告)日：2007-06-05
申请号：US11253869
申请日：2005-10-18
IPC分类号： C12N15/11
CPC分类号： C12N9/6408
摘要： This invention provides a novel membrane-type serine protease (designated MT-SP1) elevated expression of which is associated with cancer. In one embodiment, this invention provides a method obtaining a prognosis or of detecting or staging a cancer in an organism. The method involves providing a biological sample from the organism and detecting the level of a membrane type serine protease 1 (MT-SP1) in the sample, where an elevated level of the membrane-type serine protease, as compared to the level of the protease in a biological sample from a normal healthy organism indicates the presence or stage of the cancer.
摘要翻译： 本发明提供了与癌症相关的新型膜型丝氨酸蛋白酶（称为MT-SP1），其表达升高。 在一个实施方案中，本发明提供了获得预后或在生物体中检测或分期癌症的方法。 该方法包括从生物体提供生物样品，并检测样品中膜型丝氨酸蛋白酶1（MT-SP1）的水平，其中与蛋白酶水平相比，膜型丝氨酸蛋白酶水平升高 来自正常健康生物体的生物样品表明癌症的存在或阶段。
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公开(公告)号：US07030231B1
公开(公告)日：2006-04-18
申请号：US09410362
申请日：1999-09-30
IPC分类号： C12N15/11
CPC分类号： C12N9/6408
摘要： This invention provides a novel membrane-type serine protease (designated MT-SP1) elevated expression of which is associated with cancer. In one embodiment, this invention provides a method obtaining a prognosis or of detecting or staging a cancer in an organism. The method involves providing a biological sample from the organism and detecting the level of a membrane type serine protease 1 (MT-SP1) in the sample, where an elevated level of the membrane-type serine protease, as compared to the level of the protease in a biological sample from a normal healthy organism indicates the presence or stage of the cancer.
摘要翻译： 本发明提供了与癌症相关的新型膜型丝氨酸蛋白酶（称为MT-SP1），其表达升高。 在一个实施方案中，本发明提供了获得预后或在生物体中检测或分期癌症的方法。 该方法包括从生物体提供生物样品，并检测样品中膜型丝氨酸蛋白酶1（MT-SP1）的水平，其中与蛋白酶水平相比，膜型丝氨酸蛋白酶水平升高 来自正常健康生物体的生物样品表明癌症的存在或阶段。
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4.发明授权Kaposi's Syndrome Herpesvirus protease and assembly protein compositions and methods 失效卡波西综合征疱疹病毒蛋白酶和组装蛋白的组成和方法
公开(公告)号：US6033894A
公开(公告)日：2000-03-07
申请号：US64703
申请日：1998-04-22
CPC分类号： C07K14/005 , C12N9/503 , A61K38/00 , C12N2710/16422 , C12N2799/026
摘要： Kaposi's Sarcoma Herpesvirus (KSHV) protease and assembly protein sequences are disclosed. Also disclosed are polynucleotides that encode the protease and assembly protein. The invention includes screening and detection methods, as well as KSHV protease inhibitory compositions.
摘要翻译： 公开了卡波西肉瘤疱疹病毒（KSHV）蛋白酶和组装蛋白序列。 还公开了编码蛋白酶和组装蛋白的多核苷酸。 本发明包括筛选和检测方法，以及KSHV蛋白酶抑制组合物。
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公开(公告)号：US07629437B2
公开(公告)日：2009-12-08
申请号：US10686884
申请日：2003-10-15
CPC分类号： C12Q1/37 , C07K1/047 , C07K5/101 , C07K5/1024
摘要： A method is presented for the preparation and use of fluorogenic peptide substrates that allows for the configuration of general substrate libraries to rapidly identify the primary and extended specificity of enzymes, such as proteases. The substrates contain a fluorogenic-leaving group, such as 7-amino-4-carbamoylmethyl-coumarin (ACC). Substrates incorporating the ACC leaving group show comparable kinetic profiles as those with the traditionally used 7-amino-4-methyl-coumarin (AMC) leaving group. The bifunctional nature of ACC allows for the efficient production of single substrates and substrate libraries using solid-phase synthesis techniques.
摘要翻译： 提出了一种用于制备和使用荧光肽底物的方法，其允许构建一般底物文库以快速鉴定酶（例如蛋白酶）的主要和延伸的特异性。 底物含有荧光离去基团，如7-氨基-4-氨基甲酰甲基香豆素（ACC）。 结合ACC离去基团的底物显示与传统使用的7-氨基-4-甲基香豆素（AMC）离去基团相似的动力学曲线。 ACC的双功能特性允许使用固相合成技术有效地生产单个底物和底物文库。
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6.发明授权公开(公告)号：US06680178B2
公开(公告)日：2004-01-20
申请号：US09866132
申请日：2001-05-25
IPC分类号： C12Q137
CPC分类号： C12Q1/37 , C07K1/047 , C07K5/101 , C07K5/1024
摘要： A method is presented for the preparation and use of fluorogenic peptide substrates that allows for the configuration of general substrate libraries to rapidly identify the primary and extended specificity of enzymes, such as proteases. The substrates contain a fluorogenic-leaving group, such as 7-amino-4-carbamoylmethyl-coumarin (ACC). Substrates incorporating the ACC leaving group show comparable kinetic profiles as those with the traditionally used 7-amino-4-methyl-coumarin (AMC) leaving group. The bifunctional nature of ACC allows for the efficient production of single substrates and substrate libraries using solid-phase synthesis techniques. The approximately 3-fold increased quantum yield of ACC over AMC permits reduction in enzyme and substrate concentrations. As a consequence, a greater number of substrates can be tolerated in a single assay, thus enabling an increase in the diversity space of the library. Soluble positional protease substrate libraries of 137,180 and 6,859 members, possessing amino acid diversity at the P4-P3-P2-P1 and P4-P3-P2 positions, respectively, were constructed. Employing this screening method the substrate specificities of a diverse array of proteases were profiled, including the serine proteases thrombin, plasmin, factor Xa, uPA, tPA, granzyme B, trypsin, chymotrypsin, human neutrophil elastase, and the cysteine proteases papain and cruzain. The resulting profiles create a pharmacophoric portrayal of the proteases allowing for the design of selective substrates and potent inhibitors.
摘要翻译： 提出了一种用于制备和使用荧光肽底物的方法，其允许构建一般底物文库以快速鉴定酶（例如蛋白酶）的主要和延伸的特异性。 底物含有荧光离去基团，如7-氨基-4-氨基甲酰甲基香豆素（ACC）。 结合ACC离去基团的底物显示与传统使用的7-氨基-4-甲基香豆素（AMC）离去基团相似的动力学曲线。 ACC的双功能特性允许使用固相合成技术有效地生产单个底物和底物文库。 ACC超过AMC的大约3倍增加的量子产率允许酶和底物浓度的降低。 因此，在单个测定中可以容忍更多数量的底物，从而能够增加文库的多样性空间。 构建了分别在P4-P3-P2-P1和P4-P3-P2位置具有氨基酸多样性的137,180和6,859个成员的可溶性位置蛋白酶底物文库。 使用这种筛选方法，分析各种蛋白酶的底物特异性，包括丝氨酸蛋白酶凝血酶，纤溶酶，因子Xa，uPA，tPA，粒酶B，胰蛋白酶，胰凝乳蛋白酶，人嗜中性粒细胞弹性蛋白酶和半胱氨酸蛋白酶木瓜蛋白酶和克鲁津。 所得的谱产生蛋白酶的药效学描述，允许设计选择性底物和有效的抑制剂。
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公开(公告)号：US5747322A
公开(公告)日：1998-05-05
申请号：US650129
申请日：1996-05-09
CPC分类号： C12N9/6408 , Y10S530/857
摘要： An isolated sequence is provided that encodes crab procollagenase (Seq ID NO 5) that upon cleaving off the 29 amino acid propeptide (Seq ID NO 6) transforms into an active collagenase (Seq ID NO 4). The procollagenase has the MW of about 26.6 kD and the mature collagenase has a MW of 23.5 kD. Procollagenase mutated at positions 201 and 235 is also provided. A storage-stabilized composition providing long-term, shelf-stable protease that can be readily activated when collagenolytic activity is desired is disclosed.
摘要翻译： 提供了分离的序列，其编码在分解出29个氨基酸前肽（Seq ID NO 6）后转化成活性胶原酶（Seq ID NO 4）的螃蟹前胶原酶（Seq ID NO 5）。 原胶原酶具有约26.6kD的MW，成熟胶原酶的MW为23.5kD。 还提供在201和235位突变的原胶原酶。 公开了一种储存稳定的组合物，其提供长期的，稳定的蛋白酶，当需要胶原分解活性时可以容易地活化。
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公开(公告)号：US5583000A
公开(公告)日：1996-12-10
申请号：US122792
申请日：1993-09-16
申请人： Paul R. Ortiz de Montellano , Irwin D. Kuntz , Charles S. Craik , Paul S. Furth , Juan C. Alvarez , Patricia S. Caldera , Dianne L. DeCamp , Lilia M. Bab e , James De Voss , Rafael Salto , Zhihua Sui
发明人： Paul R. Ortiz de Montellano , Irwin D. Kuntz , Charles S. Craik , Paul S. Furth , Juan C. Alvarez , Patricia S. Caldera , Dianne L. DeCamp , Lilia M. Bab e , James De Voss , Rafael Salto , Zhihua Sui
IPC分类号： A61K31/047 , A61K31/12 , A61K31/436 , A61K31/4425 , A61K31/444 , A61K31/451 , A61K31/452 , A61K31/4525 , A61K31/453 , A61K31/4535 , A61K31/4709 , C07D211/52 , G01N33/573 , A61K31/44 , A61K31/445 , A61K31/47
CPC分类号： G01N33/573 , A61K31/047 , A61K31/12 , A61K31/436 , A61K31/4425 , A61K31/444 , A61K31/451 , A61K31/452 , A61K31/4525 , A61K31/453 , A61K31/4535 , A61K31/4709 , C07D211/52
摘要： Non-peptide, protease-binding compounds are described as useful in the detection, labelling, and inhibition of retroviral proteases. Aryl piperidinyl derivatives and other compounds related in structure have been found to be HIV-1 and HIV-2 protease-binding compounds.
摘要翻译： 描述了非肽，蛋白酶结合化合物可用于检测，标记和抑制逆转录病毒蛋白酶。 已经发现芳基哌啶基衍生物和结构相关的其它化合物是HIV-1和HIV-2蛋白酶结合化合物。
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公开(公告)号：US20120141373A1
公开(公告)日：2012-06-07
申请号：US13319036
申请日：2010-05-04
IPC分类号： A61K51/10 , G01N33/567 , C07H21/04 , C12N9/99 , C07K16/40 , A61K39/395 , G01N33/573
CPC分类号： C07K16/40 , A61K38/00 , A61K51/1075 , A61K2039/505 , C07K2317/21 , C07K2317/55 , C07K2317/56 , C07K2317/565 , C07K2317/76 , C12Q1/37 , G01N33/574 , G01N2333/95 , G01N2500/04
摘要： The disclosure relates to protease-binding agent specific for a protease. The agent may be an antibody capable of specifically binding and inhibiting a protease, such as a P1-Arg-specific protease. The disclosure also provides methods of producing, and compositions comprising the subject agent. Methods and kits related to the protease-binding agent find use in protection against, detection, diagnosing, treating cancer and infections due to pathogens containing active proteases.
摘要翻译： 本公开涉及对蛋白酶特异性的蛋白酶结合剂。 该试剂可以是能够特异性结合和抑制蛋白酶例如P1-Arg特异性蛋白酶的抗体。 本公开还提供了生产方法和包含该主题试剂的组合物。 与蛋白酶结合剂相关的方法和试剂盒可用于保护，检测，诊断，治疗癌症和由于含有活性蛋白酶的病原体引起的感染。
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10.发明授权公开(公告)号：US06534310B1
公开(公告)日：2003-03-18
申请号：US09587577
申请日：2000-06-01
申请人： Charles S. Craik , Lilia M. Babé , Jason Rosé
发明人： Charles S. Craik , Lilia M. Babé , Jason Rosé
IPC分类号： C12N500
CPC分类号： A61K38/162 , A61K48/00 , C12N9/506 , C12N2799/027
摘要： The present invention provides recombinant vectors comprising polynucleotides encoding defective monomers of HIV (e.g., HIV-1 or HIV-2) protease which are used to interfere with viral maturation. The defective monomers result in the formation of inactive protease heterodimers and thus inhibit the polyprotein processing events that are essential for viral maturation and infectivity.
摘要翻译： 本发明提供了包含用于干扰病毒成熟的编码HIV缺陷单体（例如，HIV-1或HIV-2）蛋白酶的多核苷酸的重组载体。 有缺陷的单体导致无活性蛋白酶异二聚体的形成，从而抑制对于病毒成熟和感染性至关重要的多蛋白加工事件。
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