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公开(公告)号:US20060041105A1
公开(公告)日:2006-02-23
申请号:US11133804
申请日:2005-05-19
申请人: Tao Jiang , Emilia Olson , Michael Whitney , Roger Tsien
发明人: Tao Jiang , Emilia Olson , Michael Whitney , Roger Tsien
IPC分类号: A61K38/12
CPC分类号: C07K7/08 , A61K38/00 , A61K41/0095 , A61K47/64 , A61K47/645 , A61K47/65 , A61K49/0032 , A61K49/0043 , A61K49/0056 , A61K49/085 , A61K49/14 , A61K49/146 , A61K51/088 , C07K14/00 , C07K14/4728
摘要: A generic structure for the peptides of the present invention includes A-X-B-C, where C is a cargo moiety, the B portion includes basic amino acids, X is a cleavable linker sequence, and the A portion includes acidic amino acids. The intact structure is not significantly taken up by cells; however, upon extracellular cleavage of X, the B-C portion is taken up, delivering the cargo to targeted cells. Cargo may be, for example, a contrast agent for diagnostic imaging, a chemotherapeutic drug, or a radiation-sensitizer for therapy. X may be cleaved extracellularly or intracellularly. The molecules of the present inventnon may be linear, cyclic, branched, or have a mixed structure.
摘要翻译: 本发明的肽的一般结构包括A-X-B-C,其中C是货物部分,B部分包括碱性氨基酸,X是可切割的接头序列,A部分包括酸性氨基酸。 完整结构不被细胞所占据; 然而,在X的细胞外裂解时,B-C部分被吸收,将货物运送到靶细胞。 货物可以是例如用于诊断成像的对比剂,化学治疗药物或用于治疗的放射线敏化剂。 X可能在细胞外或细胞内裂解。 本发明的分子可以是直链,环状,支链或具有混合结构。
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公开(公告)号:US09808532B2
公开(公告)日:2017-11-07
申请号:US13384581
申请日:2010-07-15
申请人: Roger Tsien , Emilia Olson , Tao Jiang , Quyen Nguyen , Michael Whitney
发明人: Roger Tsien , Emilia Olson , Tao Jiang , Quyen Nguyen , Michael Whitney
CPC分类号: A61K47/64 , A61K47/595 , A61K47/60 , A61K47/62 , A61K47/6911 , A61K49/0032 , A61K49/0056 , C07K7/06
摘要: Disclosed herein, in certain embodiments, is a selective transport molecule with increased in vivo circulation. In some embodiments, a selective transport molecule disclosed herein has the formula (A-X-B-C)n-M, wherein C is a cargo moiety; A is a peptide with a sequence comprising 5 to 9 consecutive acidic amino acids, wherein the amino acids are selected from: aspartates and glutatmates; B is a peptide with a sequence comprising 5 to 20 consecutive basic amino acids; X is a linker; and M is a macromolecular carrier.
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公开(公告)号:US07985401B2
公开(公告)日:2011-07-26
申请号:US11133804
申请日:2005-05-19
申请人: Tao Jiang , Emilia S. Olson , Michael Whitney , Roger Tsien
发明人: Tao Jiang , Emilia S. Olson , Michael Whitney , Roger Tsien
CPC分类号: C07K7/08 , A61K38/00 , A61K41/0095 , A61K47/64 , A61K47/645 , A61K47/65 , A61K49/0032 , A61K49/0043 , A61K49/0056 , A61K49/085 , A61K49/14 , A61K49/146 , A61K51/088 , C07K14/00 , C07K14/4728
摘要: A generic structure for the peptides of the present invention includes A-X-B-C, where C is a cargo moiety, the B portion includes basic amino acids, X is a cleavable linker sequence, and the A portion includes acidic amino acids. The intact structure is not significantly taken up by cells; however, upon extracellular cleavage of X, the B-C portion is taken up, delivering the cargo to targeted cells. Cargo may be, for example, a contrast agent for diagnostic imaging, a chemotherapeutic drug, or a radiation-sensitizer for therapy. X may be cleaved extracellularly or intracellularly. The molecules of the present invention may be linear, cyclic, branched, or have a mixed structure.
摘要翻译: 本发明的肽的一般结构包括A-X-B-C,其中C是货物部分,B部分包括碱性氨基酸,X是可切割的接头序列,A部分包括酸性氨基酸。 完整结构不被细胞所占据; 然而,在X的细胞外裂解时,B-C部分被吸收,将货物运送到靶细胞。 货物可以是例如用于诊断成像的对比剂,化学治疗药物或用于治疗的放射线敏化剂。 X可能在细胞外或细胞内裂解。 本发明的分子可以是直链,环状,支链或具有混合结构。
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公开(公告)号:US09072792B2
公开(公告)日:2015-07-07
申请号:US13155168
申请日:2011-06-07
申请人: Tao Jiang , Emilia S. Olson , Michael Whitney , Roger Tsien
发明人: Tao Jiang , Emilia S. Olson , Michael Whitney , Roger Tsien
IPC分类号: A61K51/00 , A61M36/14 , A61K47/48 , A61K41/00 , A61K49/00 , A61K49/08 , A61K49/14 , A61K51/08 , C07K14/47
CPC分类号: C07K7/08 , A61K38/00 , A61K41/0095 , A61K47/64 , A61K47/645 , A61K47/65 , A61K49/0032 , A61K49/0043 , A61K49/0056 , A61K49/085 , A61K49/14 , A61K49/146 , A61K51/088 , C07K14/00 , C07K14/4728
摘要: A generic structure for the peptides of the present invention includes A-X-B-C, where C is a cargo moiety, the B portion includes basic amino acids, X is a cleavable linker sequence, and the A portion includes acidic amino acids. The intact structure is not significantly taken up by cells; however, upon extracellular cleavage of X, the B-C portion is taken up, delivering the cargo to targeted cells. Cargo may be, for example, a contrast agent for diagnostic imaging, a chemotherapeutic drug, or a radiation-sensitizer for therapy. X may be cleaved extracellularly or intracellularly. The molecules of the present invention may be linear, cyclic, branched, or have a mixed structure.
摘要翻译: 本发明的肽的一般结构包括A-X-B-C,其中C是货物部分,B部分包括碱性氨基酸,X是可切割的接头序列,A部分包括酸性氨基酸。 完整结构不被细胞所占据; 然而,在X的细胞外裂解时,B-C部分被吸收,将货物运送到靶细胞。 货物可以是例如用于诊断成像的对比剂,化学治疗药物或用于治疗的放射线敏化剂。 X可能在细胞外或细胞内裂解。 本发明的分子可以是直链,环状,支链或具有混合结构。
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公开(公告)号:US20070041904A1
公开(公告)日:2007-02-22
申请号:US11437095
申请日:2006-05-19
申请人: Tao Jiang , Emilia Olsen , Michael Whitney , Todd Aguilera , Quyen Nguyen , Edmund Wong , Roger Tsien
发明人: Tao Jiang , Emilia Olsen , Michael Whitney , Todd Aguilera , Quyen Nguyen , Edmund Wong , Roger Tsien
CPC分类号: C07K7/08 , A61K38/00 , A61K41/0095 , A61K47/64 , A61K47/645 , A61K47/65 , A61K49/0032 , A61K49/0043 , A61K49/0056 , A61K49/085 , A61K49/14 , A61K49/146 , A61K51/088 , C07K14/00 , C07K14/4728
摘要: A generic structure for the peptides of the present invention includes A-X-B-C, where C is a cargo moiety, the B portion includes basic amino acids, X is a cleavable linker sequence, and the A portion includes acidic amino acids. The intact structure is not significantly taken up by cells; however, upon extracellular cleavage of X, the B-C portion is taken up, delivering the cargo to targeted cells. Cargo may be, for example, a contrast agent for diagnostic imaging, a chemotherapeutic drug, or a radiation-sensitizer for therapy. X may be cleaved extracellularly or intracellularly. The molecules of the present invention may be linear, cyclic, branched, or have a mixed structure.
摘要翻译: 本发明的肽的一般结构包括A-X-B-C,其中C是货物部分,B部分包括碱性氨基酸,X是可切割的接头序列,A部分包括酸性氨基酸。 完整结构不被细胞所占据; 然而,在X的细胞外裂解时,B-C部分被吸收,将货物运送到靶细胞。 货物可以是例如用于诊断成像的对比剂,化学治疗药物或用于治疗的放射线敏化剂。 X可能在细胞外或细胞内裂解。 本发明的分子可以是直链,环状,支链或具有混合结构。
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公开(公告)号:US20120014873A1
公开(公告)日:2012-01-19
申请号:US13155168
申请日:2011-06-07
申请人: Tao Jiang , Emilia S. Olson , Michael Whitney , Roger Y. Tsien
发明人: Tao Jiang , Emilia S. Olson , Michael Whitney , Roger Y. Tsien
IPC分类号: A61K38/12 , C07K14/00 , C07K19/00 , C12N5/071 , A61K51/08 , C07K17/00 , A61P35/00 , C07K4/00 , A61K38/16
CPC分类号: C07K7/08 , A61K38/00 , A61K41/0095 , A61K47/64 , A61K47/645 , A61K47/65 , A61K49/0032 , A61K49/0043 , A61K49/0056 , A61K49/085 , A61K49/14 , A61K49/146 , A61K51/088 , C07K14/00 , C07K14/4728
摘要: A generic structure for the peptides of the present invention includes A-X-B-C, where C is a cargo moiety, the B portion includes basic amino acids, X is a cleavable linker sequence, and the A portion includes acidic amino acids. The intact structure is not significantly taken up by cells; however, upon extracellular cleavage of X, the B-C portion is taken up, delivering the cargo to targeted cells. Cargo may be, for example, a contrast agent for diagnostic imaging, a chemotherapeutic drug, or a radiation-sensitizer for therapy. X may be cleaved extracellularly or intracellularly. The molecules of the present invention may be linear, cyclic, branched, or have a mixed structure.
摘要翻译: 本发明的肽的一般结构包括A-X-B-C,其中C是货物部分,B部分包括碱性氨基酸,X是可切割的接头序列,A部分包括酸性氨基酸。 完整结构不被细胞所占据; 然而,在X的细胞外裂解时,B-C部分被吸收,将货物运送到靶细胞。 货物可以是例如用于诊断成像的对比剂,化学治疗药物或用于治疗的放射线敏化剂。 X可能在细胞外或细胞内裂解。 本发明的分子可以是直链,环状,支链或具有混合结构。
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公开(公告)号:US20080227129A1
公开(公告)日:2008-09-18
申请号:US11821562
申请日:2007-06-22
申请人: Jeffrey Stack , Michael Whitney , Andrew B. Cubitt , Brian Pollok
发明人: Jeffrey Stack , Michael Whitney , Andrew B. Cubitt , Brian Pollok
IPC分类号: C12Q1/66 , C12Q1/02 , C12Q1/37 , C12Q1/48 , C12N1/16 , C07K14/00 , C12N5/06 , C12N5/00 , C12Q1/42 , C12Q1/34
CPC分类号: C12Q1/485
摘要: This invention is directed towards methods of destabilizing proteins in living cells, and their use for the development of novel assays. In one embodiment, the invention comprises the use of non-cleavable multimerized ubiquitin fusion proteins to destabilize a target protein, such as a reporter moiety. In one aspect of this method the constructs also comprises a linker that operatively couples the reporter moiety to the multimerized ubiquitin fusion protein. In this embodiment, enzymatic modification of the linker results in a modulation of the coupling of the reporter protein to the multimerized ubiquitin domains resulting in a change in the stability of the reporter moiety. The level of the reporter moiety in the cell can then be used as a measure of the enzymatic activity in the cell. In another embodiment the invention provides for a generalized way of coordinately regulating the cellular concentration of a plurality of target proteins. In one aspect of this method, the target proteins are operatively coupled to a ubiquitin fusion protein via a linker containing a protease cleavage site. Cleavage of the linker by a protease results in uncoupling of the target protein from the multimerized ubiquitin construct, and results in an increase in the stability and concentration of the target protein.
摘要翻译: 本发明涉及使活细胞中的蛋白质失稳的方法及其用于开发新的测定方法。 在一个实施方案中,本发明包括使用不可切割的多聚化泛素融合蛋白来使目标蛋白如报道分子部分不稳定。 在该方法的一个方面,构建体还包含使报道部分与多聚化泛素融合蛋白可操作地连接的接头。 在该实施方案中,接头的酶修饰导致报道蛋白与多聚泛素结构域的偶联的调节,导致报道部分稳定性的变化。 然后可以将细胞中的报告物部分的水平用作细胞中酶活性的量度。 在另一个实施方案中,本发明提供了协调调节多种靶蛋白的细胞浓度的一般化方式。 在该方法的一个方面,靶蛋白通过含有蛋白酶切割位点的接头与泛素融合蛋白可操作地偶联。 通过蛋白酶切割接头导致靶蛋白与多聚化泛素构建体解偶联,并导致靶蛋白的稳定性和浓度增加。
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公开(公告)号:US20110191873A1
公开(公告)日:2011-08-04
申请号:US12938179
申请日:2010-11-02
申请人: Jeffrey Stack , Michael Whitney , Andrew B. Cubitt , Brian Pollok
发明人: Jeffrey Stack , Michael Whitney , Andrew B. Cubitt , Brian Pollok
IPC分类号: A01K67/00 , C12N5/10 , C07H21/04 , C12N1/00 , C07K19/00 , A01H5/00 , C12Q1/02 , C12Q1/37 , C12Q1/42 , C12Q1/48 , C12Q1/66 , C12N5/07 , C12N5/071 , C12N5/04
CPC分类号: C12Q1/485
摘要: This invention is directed towards methods of destabilizing proteins in living cells, and their use for the development of novel assays. In one embodiment, the invention comprises the use of non-cleavable multimerized ubiquitin fusion proteins to destabilize a target protein, such as a reporter moiety. In one aspect of this method the constructs also comprises a linker that operatively couples the reporter moiety to the multimerized ubiquitin fusion protein. In this embodiment, enzymatic modification of the linker results in a modulation of the coupling of the reporter protein to the multimerized ubiquitin domains resulting in a change in the stability of the reporter moiety. The level of the reporter moiety in the cell can then be used as a measure of the enzymatic activity in the cell. In another embodiment the invention provides for a generalized way of coordinately regulating the cellular concentration of a plurality of target proteins. In one aspect of this method, the target proteins are operatively coupled to a ubiquitin fusion protein via a linker containing a protease cleavage site. Cleavage of the linker by a protease results in uncoupling of the target protein from the multimerized ubiquitin construct, and results in an increase in the stability and concentration of the target protein.
摘要翻译: 本发明涉及使活细胞中的蛋白质失稳的方法及其用于开发新的测定方法。 在一个实施方案中,本发明包括使用不可切割的多聚化泛素融合蛋白来使目标蛋白如报道分子部分不稳定。 在该方法的一个方面,构建体还包含使报道部分与多聚化泛素融合蛋白可操作地连接的连接体。 在该实施方案中,接头的酶修饰导致报道蛋白与多聚泛素结构域的偶联的调节,导致报道部分稳定性的变化。 然后可以将细胞中的报告物部分的水平用作细胞中酶活性的量度。 在另一个实施方案中,本发明提供了协调调节多种靶蛋白的细胞浓度的一般化方式。 在该方法的一个方面,靶蛋白通过含有蛋白酶切割位点的接头与泛素融合蛋白可操作地偶联。 通过蛋白酶切割接头导致靶蛋白与多聚化泛素构建体解偶联,并导致靶蛋白的稳定性和浓度增加。
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公开(公告)号:US07262005B1
公开(公告)日:2007-08-28
申请号:US09498098
申请日:2000-02-04
申请人: Jeffrey Stack , Michael Whitney , Andrew B. Cubitt , Brian Pollok
发明人: Jeffrey Stack , Michael Whitney , Andrew B. Cubitt , Brian Pollok
IPC分类号: C12Q1/68
CPC分类号: C12Q1/485
摘要: This invention is directed towards methods of destabilizing proteins in living cells, and their use for the development of novel assays. In one embodiment, the invention comprises the use of non-cleavable multimerized ubiquitin fusion proteins to destabilize a target protein, such as a reporter moiety. In one aspect of this method the constructs also comprises a linker that operatively couples the reporter moiety to the multimerized ubiquitin fusion protein. In this embodiment, enzymatic modification of the linker results in a modulation of the coupling of the reporter protein to the multimerized ubiquitin domains resulting in a change in the stability of the reporter moiety. The level of the reporter moiety in the cell can then be used as a measure of the enzymatic activity in the cell. In another embodiment the invention provides for a generalized way of coordinately regulating the cellular concentration of a plurality of target proteins. In one aspect of this method, the target proteins are operatively coupled to a ubiquitin fusion protein via a linker containing a protease cleavage site. Cleavage of the linker by a protease results in uncoupling of the target protein from the multimerized ubiquitin construct, and results in an increase in the stability and concentration of the target protein.
摘要翻译: 本发明涉及使活细胞中的蛋白质失稳的方法及其用于开发新的测定方法。 在一个实施方案中,本发明包括使用不可切割的多聚化泛素融合蛋白来使目标蛋白如报道分子部分不稳定。 在该方法的一个方面,构建体还包含使报道部分与多聚化泛素融合蛋白可操作地连接的接头。 在该实施方案中,接头的酶修饰导致报道蛋白与多聚泛素结构域的偶联的调节,导致报道部分稳定性的变化。 然后可以将细胞中的报告物部分的水平用作细胞中酶活性的量度。 在另一个实施方案中,本发明提供了协调调节多种靶蛋白的细胞浓度的一般化方式。 在该方法的一个方面,靶蛋白通过含有蛋白酶切割位点的接头与泛素融合蛋白可操作地偶联。 通过蛋白酶切割接头导致靶蛋白与多聚化泛素构建体解偶联,并导致靶蛋白的稳定性和浓度增加。
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公开(公告)号:US20050065173A1
公开(公告)日:2005-03-24
申请号:US10869498
申请日:2004-06-16
申请人: Jill Jarecki , Xiaocun Chen , Dennis Hurley , Lewis Makings , Mark Miller , Brian Pollok , Jeffrey Stack , Michael Whitney
发明人: Jill Jarecki , Xiaocun Chen , Dennis Hurley , Lewis Makings , Mark Miller , Brian Pollok , Jeffrey Stack , Michael Whitney
IPC分类号: A61P21/00 , C07D239/95 , A61K31/517 , A61K31/55
CPC分类号: C07D239/95
摘要: The present invention relates to compounds useful as promoters of the SMN2 gene. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of Spinal Muscular Atrophy.
摘要翻译: 本发明涉及可用作SMN2基因启动子的化合物。 本发明还提供包含所述化合物的药学上可接受的组合物和使用该组合物治疗脊髓性肌萎缩的方法。
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