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公开(公告)号：US07049083B2
公开(公告)日：2006-05-23
申请号：US10051843
申请日：2002-01-17
IPC分类号： C12N15/63 , C12N1/15 , C12N1/16 , C12N15/00 , G01N33/566
CPC分类号： C12Q1/025 , G01N2333/705
摘要： Methods and compositions for identifying compounds which disrupt the functional interaction of an intracellular receptor region of an α-subunit of a voltage-gated ion channel and an amino-terminal inactivation region of an ion channel protein are disclosed. Compounds that disrupt the functional or binding interaction of these two regions have significant modulatory effects on ion channel activity, and thus are likely to be useful for treating and/or preventing a wide variety of diseases and pathological conditions associated with ion channel dysfunction. Such conditions include, for example, neurological disorders, cardiac diseases, metabolic diseases, tumor-driven diseases, and autoimmune diseases.
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公开(公告)号：US06673540B1
公开(公告)日：2004-01-06
申请号：US09714258
申请日：2000-11-17
IPC分类号： C12Q168
CPC分类号： C07K14/72 , C07K14/61 , C07K2319/00 , C12Q1/6897
摘要： This invention relates to modified host cells which express heterologous fused proteins and methods of screening for test samples having peptide binding activity; wherein the modified host cell comprises: (a) a gene sequence encoding a heterologous fusion protein; the fusion protein comprising a first peptide of a peptide binding pair, or segment of the first peptide, which is joined to either a DNA binding domain or its corresponding transcriptional activation domain of a transcriptional activation protein; (b) a gene sequence encoding a heterologous fusion protein, the fusion protein comprising a second peptide of the peptide binding pair in (a), or a segment thereof, fused to either a DNA binding domain or its corresponding transcriptional activation domain, whichever one is not employed in (a); (c) a reporter gene operatively associated with the transcriptional activation protein, or a portion thereof; (d) optionally, a deletion or mutation in the chromosomal DNA of the host cell for the transcriptional activation protein if present in the selected host cell.
摘要翻译： 本发明涉及表达异源融合蛋白的修饰的宿主细胞和筛选具有肽结合活性的测试样品的方法; 其中所述修饰的宿主细胞包含：（a）编码异源融合蛋白的基因序列; 所述融合蛋白包含肽结合对的第一肽或第一肽的片段，其连接到转录激活蛋白的DNA结合结构域或其相应的转录激活结构域; （b）编码异源融合蛋白的基因序列，所述融合蛋白包含（a）中的肽结合对的第二个肽或其部分融合到DNA结合结构域或其相应的转录激活结构域，无论哪个 （a）没有雇用; （c）与转录激活蛋白有效相关的报告基因，或其一部分; （d）任选地，如果存在于所选择的宿主细胞中，则转录激活蛋白的宿主细胞的染色体DNA中的缺失或突变。
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公开(公告)号：US06251602B1
公开(公告)日：2001-06-26
申请号：US09263944
申请日：1999-03-08
IPC分类号： C12Q168
CPC分类号： C07K14/72 , C07K14/61 , C07K2319/00 , C12Q1/6897
摘要： This invention relates to novel modified host cells which express heterologous fused proteins and methods of screening for test samples having peptide-binding activity; wherein the modified host cell comprises: (a) a gene sequence encoding a heterologous fusion protein; said fusion protein comprising a first peptide of a peptide binding pair, or segment of said first peptide, which is joined to either a DNA binding domain or its corresponding transcriptional activation domain of a transcriptional activation protein; (b) a gene sequence encoding a heterologous fusion protein, said fusion protein comprising a second peptide of the peptide binding pair in (a), or a segment thereof, fused to either a DNA binding domain or its corresponding transcriptional activation domain, whichever one is not employed in (a); (c) a reporter gene operatively associated with the transcriptional activation protein, or a portion thereof; (d) optionally, a deletion or mutation in the chromosomal DNA of the host cell for the transcriptional activation protein if present in the selected host cell.
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4.发明授权Identification of compounds affecting specific interaction of peptide binding pairs 失效鉴定影响肽结合对特异性相互作用的化合物
公开(公告)号：US5989808A
公开(公告)日：1999-11-23
申请号：US259609
申请日：1994-06-14
CPC分类号： C07K14/72 , C07K14/61 , C12Q1/6897 , C07K2319/00
摘要： This invention relates to novel modified host cells which express heterologous fused proteins and methods of screening for test samples having peptide-binding activity; wherein the modified host cell comprises: (a) a gene sequence encoding a heterologous fusion protein; said fusion protein comprising a first peptide of a peptide binding pair, or segment of said first peptide, which is joined to either a DNA binding domain or its corresponding transcriptional activation domain of a transcriptional activation protein; (b) a gene sequence encoding a heterologous fusion protein, said fusion protein comprising a second peptide of the peptide binding pair in (a), or a segment thereof, fused to either a DNA binding domain or its corresponding transcriptional activation domain, whichever one is not employed in (a); (c) a reporter gene operatively associated with the transcriptional activation protein, or a portion thereof; (d) optionally, a deletion or mutation in the chromosomal DNA of the host cell for the transcriptional activation protein if present in the selected host cell.
摘要翻译： 本发明涉及表达异源融合蛋白的新型修饰宿主细胞和筛选具有肽结合活性的测试样品的方法; 其中所述修饰的宿主细胞包含：（a）编码异源融合蛋白的基因序列; 所述融合蛋白包含肽结合对的第一肽或所述第一肽的片段，其连接到转录激活蛋白的DNA结合结构域或其相应的转录激活结构域; （b）编码异源融合蛋白的基因序列，所述融合蛋白包含（a）中的肽结合对的第二个肽或其部分融合到DNA结合结构域或其相应的转录激活结构域，无论哪个 （a）没有雇用; （c）与转录激活蛋白有效相关的报告基因，或其一部分; （d）任选地，如果存在于所选择的宿主细胞中，则转录激活蛋白的宿主细胞的染色体DNA中的缺失或突变。
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公开(公告)号：US06664068B2
公开(公告)日：2003-12-16
申请号：US10116370
申请日：2002-04-04
申请人： Robert Mark , Kathleen H. Young , Andrew T. Wood
发明人： Robert Mark , Kathleen H. Young , Andrew T. Wood
IPC分类号： G01N3353
CPC分类号： C07K14/4747 , A61K38/00 , A61K48/00 , C07K2319/00
摘要： The present invention relates, at least in part, to polypeptides which include Bcl-xL binding domains, novel Bcl-xL binding domains of Pablo polypeptides, nucleic acid molecules encoding such polypeptides, and uses thereof. For example, such polypeptides and nucleic acid molecules are useful in modulating apoptosis, particularly in neural cells, as well as in the treatment or prevention of disorders that can benefit from modulation of cell death.
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公开(公告)号：US06284519B1
公开(公告)日：2001-09-04
申请号：US09305483
申请日：1999-05-06
IPC分类号： C12N119
CPC分类号： C07K14/72 , C07K14/61 , C07K2319/00 , C12Q1/6897
摘要： This invention relates to novel modified host cells which express heterologous fused proteins and methods of screening for test samples having peptide-binding activity; wherein the modified host cell comprises: (a) a gene sequence encoding a heterologous fusion protein; said fusion protein comprising a first peptide of a peptide binding pair, or segment of said first peptide, which is joined to either a DNA binding domain or its corresponding transcriptional activation domain of a transcriptional activation protein; (b) a gene sequence encoding a heterologous fusion protein, said fusion protein comprising a second peptide of the peptide binding pair in (a), or a segment thereof, fused to either a DNA binding domain or its corresponding transcriptional activation domain, whichever one is not employed in (a); (c) a reporter gene operatively associated with the transcriptional activation protein, or a portion thereof; (d) optionally, a deletion or mutation in the chromosomal DNA of the host cell for the transcriptional activation protein if present in the selected host cell.
摘要翻译： 本发明涉及表达异源融合蛋白的新型修饰宿主细胞和筛选具有肽结合活性的测试样品的方法; 其中所述修饰的宿主细胞包含：（a）编码异源融合蛋白的基因序列; 所述融合蛋白包含肽结合对的第一肽或所述第一肽的片段，其连接到转录激活蛋白的DNA结合结构域或其相应的转录激活结构域; （b）编码异源融合蛋白的基因序列，所述融合蛋白包含（a）中的肽结合对的第二个肽或其片段，其融合到DNA结合结构域或其相应的转录激活结构域，无论哪个 （a）没有雇用; （c）与转录激活蛋白有效相关的报告基因，或其一部分; （d）任选地，如果存在于所选择的宿主细胞中，则转录激活蛋白的宿主细胞的染色体DNA中的缺失或突变。
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公开(公告)号：US06248875B1
公开(公告)日：2001-06-19
申请号：US09064414
申请日：1998-04-22
IPC分类号： C12N1512
CPC分类号： C07K14/715
摘要： A MORT1 gene initially cloned from HeLa cells and identified as a member of the receptor mediated apoptotic pathway, is expressed in the human neuronal cell line, NTERA2. Isolation of the MORT1 from this cell line revealed a transcript isoform that differed from the known MORT1 sequence by a deletion of 21 base pairs (bp 172-192 of the coding sequence). Cloning of MORT1 from adult human brain revealed two isoforms, one similarly deleted for bp 172-192, the other with a basepair substitution, A for G at position 173. Assessment of MORT1 function in a yeast two hybrid system indicates that the deleted and intact forms of MORT1 differ in their capacity to interact with other members of the apoptotic pathway.
摘要翻译： 最初由HeLa细胞克隆并鉴定为受体介导的凋亡通路的成员的MORT1基因在人神经元细胞系NTERA2中表达。 从该细胞系分离MORT1显示了与已知MORT1序列不同的转录本同工型，其缺失21个碱基对（编码序列的bp172-192）。 从成年人脑中克隆MORT1显示两种同种型，一种类似于bp 172-192缺失，另一种具有碱基取代，A位于173位。酵母双杂交体系中MORT1功能的评估表明，缺失和完整 MORT1的形式与其他凋亡途径成员的相互作用不同。
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公开(公告)号：US07049094B2
公开(公告)日：2006-05-23
申请号：US10051841
申请日：2002-01-17
CPC分类号： C12Q1/025 , G01N2333/705
摘要： Methods and compositions for identifying compounds which disrupt the functional interaction of an intracellular receptor region of an α-subunit of a voltage-gated ion channel and an amino-terminal inactivation region of an ion channel protein are disclosed. Compounds that disrupt the functional or binding interaction of these two regions have significant modulatory effects on ion channel activity, and thus are likely to be useful for treating and/or preventing a wide variety of diseases and pathological conditions associated with ion channel dysfunction. Such conditions include, for example, neurological disorders, cardiac diseases, metabolic diseases, tumor-driven diseases, and autoimmune diseases.
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公开(公告)号：US06770446B1
公开(公告)日：2004-08-03
申请号：US09556390
申请日：2000-04-24
申请人： Kathleen H. Young , Jian Cao
发明人： Kathleen H. Young , Jian Cao
IPC分类号： G01N3353
CPC分类号： C07K14/72 , C07K14/61 , C07K2319/00 , C12Q1/6897
摘要： This invention relates to novel modified host cells which express heterologous fused proteins and methods of screening for test samples having peptide-binding activity; wherein the modified host cell comprises: (a) a gene sequence encoding a heterologous fusion protein; said fusion protein comprising a first peptide of a peptide binding pair, or segment of said first peptide, which is joined to either a DNA binding domain or its corresponding transcriptional activation domain of a transcriptional activation protein; (b) a gene sequence encoding a heterologous fusion protein, said fusion protein comprising a second peptide of the peptide binding pair in (a), or a segment thereof, fused to either a DNA binding domain or its corresponding transcriptional activation domain, whichever one is not employed in (a); (c) a luciferase gene operatively associated with the transcriptional activation protein, or a portion thereof; (d) optionally, a deletion or mutation in the chromosomal DNA of the host cell for the transcriptional activation protein if present in the selected host cell.
摘要翻译： 本发明涉及表达异源融合蛋白的新型修饰宿主细胞和筛选具有肽结合活性的测试样品的方法; 其中所述修饰的宿主细胞包含：（a）编码异源融合蛋白的基因序列; 所述融合蛋白包含肽结合对的第一肽或所述第一肽的片段，其连接到转录激活蛋白的DNA结合结构域或其相应的转录激活结构域; （b）编码异源融合蛋白的基因序列，所述融合蛋白包含（a）中的肽结合对的第二个肽或其片段，其融合到DNA结合结构域或其相应的转录激活结构域，无论哪个 （a）没有雇用; （c）与转录激活蛋白有效相关的荧光素酶基因，或其一部分; （d）任选地，如果存在于所选择的宿主细胞中，则转录激活蛋白的宿主细胞的染色体DNA中的缺失或突变。
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