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1. 发明授权

US5955453A Membrane-permeant phosphoinositides 失效
标题翻译：膜透性磷酸肌醇
公开(公告)号：US5955453A
公开(公告)日：1999-09-21
申请号：US066037
申请日：1998-04-24
申请人： Roger Y. Tsien , Tao Jiang
发明人： Roger Y. Tsien , Tao Jiang
IPC分类号： C12Q1/02 , A61K31/66 , A61P43/00 , C07F9/117 , C07F9/10 , C07F9/177 , C07F9/24
CPC分类号： C07F9/117 , A61K31/66
摘要： Membrane-permeant phosphoinositides, including phosphatidylinositol phosphate esters, are described. A membrane-permeant phosphoinositide includes groups that neutralize the charges of the phosphate moieties of the phosphoinositide. A cell can be treated with the membrane-permeant phosphoinositide, which is then absorbed into the cell. The neutralizing groups can be removed intracellularly to afford the charged phosphoinositide.
摘要翻译：描述了膜 - 渗透性磷酸肌醇，包括磷脂酰肌醇磷酸酯。膜透性磷酸肌醇包括中和磷酸肌醇的磷酸酯部分的电荷的基团。可以用膜透过性磷酸肌醇治疗细胞，然后将其吸收到细胞中。可以在细胞内除去中和基团，得到带电的磷酸肌醇。

2. 发明申请

US20130078188A1 ACTIVATABLE CELL PENETRATING PEPTIDES WITH QUENCHED FLUOROPHORES 有权
标题翻译：可激活的细胞培养肽与猝灭荧光素酶
公开(公告)号：US20130078188A1
公开(公告)日：2013-03-28
申请号：US13566913
申请日：2012-08-03
申请人： Roger Y. Tsien , Tao Jiang , Elamprakash N. Savariar
发明人： Roger Y. Tsien , Tao Jiang , Elamprakash N. Savariar
IPC分类号： C07K19/00 , A61K49/00
CPC分类号： C07K19/00 , A61K41/0095 , A61K47/64 , A61K47/645 , A61K47/65 , A61K49/0032 , A61K49/0043 , A61K49/0056 , A61K49/085 , A61K49/14 , A61K49/146 , A61K51/088 , C07K14/4728
摘要： The invention provides compositions useful as molecular probes. In particular, the invention provides activatable cell penetrating peptides comprising a fluorescence donor and a fluorescence acceptor. Exemplary fluorescence donors and fluorescence acceptors include compounds derived from cyanine. Also provided are ratiometric, multispectral, and excitation lifetime imaging methods for detecting the molecular probes provided herein.
摘要翻译：本发明提供了可用作分子探针的组合物。特别地，本发明提供可激活的细胞穿透肽，其包含荧光供体和荧光受体。示例性荧光供体和荧光受体包括衍生自花青的化合物。还提供了用于检测本文提供的分子探针的比例计，多光谱和激发寿命成像方法。

3. 发明申请

US20110172139A1 PEPTIDES WHOSE UPTAKE BY CELLS IS CONTROLLABLE 有权
标题翻译：细胞摄取的肽可以控制
公开(公告)号：US20110172139A1
公开(公告)日：2011-07-14
申请号：US12244602
申请日：2008-10-02
申请人： Tao Jiang , Roger Y. Tsien
发明人： Tao Jiang , Roger Y. Tsien
IPC分类号： A61K38/02 , C07K2/00 , C12N9/96 , C12P21/06 , C07H21/00 , A61P35/00
CPC分类号： A61K49/0043 , A61K47/65 , A61K49/0056
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. Cleavage of X allows separation of A from B, unmasking the normal ability of the basic amino acids in B to drag cargo C into cells near the cleavage event. X is cleaved extracellularly, preferably under physiological conditions. D-amino acids are preferred for the A and B portions, to minimize immunogenicity and nonspecific cleavage by background peptidases or proteases.
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的裂解允许A与B分离，揭示B中碱性氨基酸的正常能力，将货物C拖入裂解事件附近的细胞。 X在细胞外裂解，优选在生理条件下。对于A和B部分，D-氨基酸是优选的，以使由背景肽酶或蛋白酶的免疫原性和非特异性切割最小化。

4. 发明授权

US07431915B2 Peptides whose uptake by cells is controllable 有权
标题翻译：细胞摄取的肽是可控的
公开(公告)号：US07431915B2
公开(公告)日：2008-10-07
申请号：US10699562
申请日：2003-10-31
申请人： Tao Jiang , Roger Y. Tsien
发明人： Tao Jiang , Roger Y. Tsien
IPC分类号： A61K51/00 , A61M36/14
CPC分类号： A61K49/0043 , A61K47/65 , A61K49/0056
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. Cleavage of X allows separation of A from B, unmasking the normal ability of the basic amino acids in B to drag cargo C into cells near the cleavage event. X is cleaved extracellularly, preferably under physiological conditions. D-amino acids are preferred for the A and B portions, to minimize immunogenicity and nonspecific cleavage by background peptidases or proteases.
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的裂解允许A与B分离，揭示B中碱性氨基酸的正常能力，将货物C拖入裂解事件附近的细胞。 X在细胞外裂解，优选在生理条件下。对于A和B部分，D-氨基酸是优选的，以使由背景肽酶或蛋白酶的免疫原性和非特异性切割最小化。

5. 发明授权

US08642561B2 Peptides whose uptake by cells is controllable 有权
标题翻译：细胞摄取的肽是可控的
公开(公告)号：US08642561B2
公开(公告)日：2014-02-04
申请号：US13314134
申请日：2011-12-07
申请人： Tao Jiang , Roger Y. Tsien
发明人： Tao Jiang , Roger Y. Tsien
IPC分类号： A61K38/06 , A61K38/16 , A61K38/10 , G01N33/533 , C07H19/04 , G03F7/00
CPC分类号： A61K49/0043 , A61K47/65 , A61K49/0056
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. Cleavage of X allows separation of A from B, unmasking the normal ability of the basic amino acids in B to drag cargo C into cells near the cleavage event. X is cleaved extracellularly, preferably under physiological conditions. D-amino acids are preferred for the A and B portions, to minimize immunogenicity and nonspecific cleavage by background peptidases or proteases.
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的裂解允许A与B分离，揭示B中碱性氨基酸的正常能力，将货物C拖入裂解事件附近的细胞。 X在细胞外裂解，优选在生理条件下。对于A和B部分，D-氨基酸是优选的，以使由背景肽酶或蛋白酶的免疫原性和非特异性切割最小化。

6. 发明授权

US09695251B2 Activatable cell penetrating peptides with quenched fluorophores 有权
公开(公告)号：US09695251B2
公开(公告)日：2017-07-04
申请号：US13566913
申请日：2012-08-03
申请人： Roger Y. Tsien , Tao Jiang , Elamprakash N. Savariar
发明人： Roger Y. Tsien , Tao Jiang , Elamprakash N. Savariar
IPC分类号： A61K51/00 , A61M36/14 , C07K19/00 , A61K49/00 , A61K41/00 , A61K47/48 , A61K49/08 , A61K49/14 , A61K51/08 , C07K14/47
CPC分类号： C07K19/00 , A61K41/0095 , A61K47/64 , A61K47/645 , A61K47/65 , A61K49/0032 , A61K49/0043 , A61K49/0056 , A61K49/085 , A61K49/14 , A61K49/146 , A61K51/088 , C07K14/4728
摘要： The invention provides compositions useful as molecular probes. In particular, the invention provides activatable cell penetrating peptides comprising a fluorescence donor and a fluorescence acceptor. Exemplary fluorescence donors and fluorescence acceptors include compounds derived from cyanine. Also provided are ratiometric, multispectral, and excitation lifetime imaging methods for detecting the molecular probes provided herein.

7. 发明申请

US20120251445A1 PEPTIDES WHOSE UPTAKE BY CELLS IS CONTROLLABLE 有权
标题翻译：细胞摄取的肽可以控制
公开(公告)号：US20120251445A1
公开(公告)日：2012-10-04
申请号：US13314134
申请日：2011-12-07
申请人： Tao Jiang , Roger Y. Tsien
发明人： Tao Jiang , Roger Y. Tsien
IPC分类号： C12N5/071 , A61K49/00 , A61K51/08 , G01N27/72 , G01N23/00 , G01N21/64 , C12Q1/02 , A61K49/14 , B82Y15/00
CPC分类号： A61K49/0043 , A61K47/65 , A61K49/0056
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. Cleavage of X allows separation of A from B, unmasking the normal ability of the basic amino acids in B to drag cargo C into cells near the cleavage event. X is cleaved extracellularly, preferably under physiological conditions. D-amino acids are preferred for the A and B portions, to minimize immunogenicity and nonspecific cleavage by background peptidases or proteases.
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的裂解允许A与B分离，揭示B中碱性氨基酸的正常能力，将货物C拖入裂解事件附近的细胞。 X在细胞外裂解，优选在生理条件下。对于A和B部分，D-氨基酸是优选的，以使由背景肽酶或蛋白酶的免疫原性和非特异性切割最小化。

8. 发明授权

US08110554B2 Peptides whose uptake by cells is controllable 有权
标题翻译：细胞摄取的肽是可控的
公开(公告)号：US08110554B2
公开(公告)日：2012-02-07
申请号：US12244602
申请日：2008-10-02
申请人： Tao Jiang , Roger Y. Tsien
发明人： Tao Jiang , Roger Y. Tsien
IPC分类号： A61K38/08 , A61K38/16 , G01N33/533 , C07H19/04 , G03F7/00
CPC分类号： A61K49/0043 , A61K47/65 , A61K49/0056
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. Cleavage of X allows separation of A from B, unmasking the normal ability of the basic amino acids in B to drag cargo C into cells near the cleavage event. X is cleaved extracellularly, preferably under physiological conditions. D-amino acids are preferred for the A and B portions, to minimize immunogenicity and nonspecific cleavage by background peptidases or proteases.
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的裂解允许A与B分离，揭示B中碱性氨基酸的正常能力，将货物C拖入裂解事件附近的细胞。 X在细胞外裂解，优选在生理条件下。对于A和B部分，D-氨基酸是优选的，以使由背景肽酶或蛋白酶的免疫原性和非特异性切割最小化。

9. 发明申请

US20120014873A1 PEPTIDES WHOSE UPTAKE BY CELLS IS CONTROLLABLE 有权
标题翻译：细胞摄取的肽可以控制
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。

10. 发明授权

US09651494B2 Fluorescent probes for monitoring voltage by photo-induced electron transfer 有权
公开(公告)号：US09651494B2
公开(公告)日：2017-05-16
申请号：US14118836
申请日：2012-05-21
申请人： Evan Walker Miller , Roger Y. Tsien
发明人： Evan Walker Miller , Roger Y. Tsien
IPC分类号： G01N21/64 , G01N33/50 , G01N33/542 , C09K11/06
CPC分类号： G01N21/6486 , C09K11/06 , C09K2211/1007 , C09K2211/1011 , C09K2211/1088 , G01N33/5008 , G01N33/542 , G01N2500/10
摘要： Compounds and methods for determining transmembrane potential, monitoring changes in transmembrane potential, and/or drug screening are provided. In one aspect, compounds of the invention have a structure according to the formula: E-M-A, wherein A is a fluorophore, selected from xanthenes, coumarins, cyanines, bimanes, and difluoroboradizaindacenes, charged at physiological pH; M is a molecular wire; and E is a hydrophobic moiety, wherein A and E are capable of being involved in a photo-induced, intramolecular electron transfer that quenches the fluorescence of A in response to a voltage condition. When in use, compounds of the invention are membrane-impermeant and oriented within the cell membrane such that the charged moiety localizes at the outer leaflet of the lipid bilayer and the hydrophobic moiety and molecular wire associate with the hydrophobic portion of the lipid bilayer. The rate of electron transfer, fluorescence intensity, and quenching are altered in response to changes in transmembrane potential.

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