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1. 发明授权

US07662644B2 Labeled peptides, proteins and antibodies and processes and intermediates useful for their preparation 失效
标题翻译：标记的肽，蛋白质和抗体以及用于其制备的方法和中间体
公开(公告)号：US07662644B2
公开(公告)日：2010-02-16
申请号：US11673909
申请日：2007-02-12
申请人： Klaus M. Hahn , Alexei Toutchkine , Rajeev Muthyala , Vadim Kraynov , Steven J. Bark , Dennis R. Burton , Chester Chamberlain
发明人： Klaus M. Hahn , Alexei Toutchkine , Rajeev Muthyala , Vadim Kraynov , Steven J. Bark , Dennis R. Burton , Chester Chamberlain
IPC分类号： G01N33/533 , G01N33/532 , G01N33/53 , C07K1/10 , C07D277/62
CPC分类号： C07K1/13 , C07K1/1077
摘要： The invention provides peptide synthons having protected functional groups for attachment of desired moieties (e.g. functional molecules or probes). Also provided are peptide conjugates prepared from such synthons, and synthon and conjugate preparation methods including procedures for identifying optimum probe attachment sites. Biosensors are provided having functional molecules that can locate and bind to specific biomolecules within living cells. Biosensors can detect chemical and physiological changes in those biomolecules as living cells are moving, metabolizing and reacting to its environment. Methods are included for detecting GTP activation of a Rho GTPase protein using polypeptide biosensors. When the biosensor binds GTP-activated Rho GTPase protein, an environmentally sensitive dye emits a signal of a different lifetime, intensity or wavelength than when not bound. New fluorophores whose fluorescence responds to environmental changes are also provided that have improved detection and attachment properties, and that can be used in living cells, or in vitro.
摘要翻译：本发明提供具有用于连接所需部分（例如功能分子或探针）的保护的官能团的肽合成子。还提供了由这种合成子制备的肽缀合物，以及合成子和缀合物制备方法，包括鉴定最佳探针附着位点的程序。生物传感器具有能够定位并结合活细胞内的特定生物分子的功能分子。生物传感器可以检测生物分子中的化学和生理变化，因为活细胞正在移动，代谢并对其环境作出反应。包括使用多肽生物传感器检测Rho GTPase蛋白的GTP活化的方法。当生物传感器结合GTP激活的Rho GTPase蛋白质时，环境敏感的染料会发出与未结合不同的寿命，强度或波长的信号。还提供了荧光对环境变化的响应的新荧光团，其具有改进的检测和附着性质，并且可用于活细胞或体外。

2. 发明授权

US07592188B2 Live cell biosensors 失效
标题翻译：活细胞生物传感器
公开(公告)号：US07592188B2
公开(公告)日：2009-09-22
申请号：US11079907
申请日：2005-03-14
申请人： Klaus M. Hahn , Alexei Toutchkine
发明人： Klaus M. Hahn , Alexei Toutchkine
IPC分类号： G01N21/91 , G01N21/64 , G01N33/533 , C09B69/00 , A61K38/00
CPC分类号： G01N33/6857 , C07D403/06 , C07D409/06 , C07D417/06 , C07D471/04 , C07K2319/60 , G01N33/542 , G01N33/573 , G01N33/582 , G01N2333/16 , G01N2333/916 , G01N2500/10 , Y10S436/80
摘要： The invention provides dyes, biosensors, and methods for using the dyes and biosensors to detect selected target molecules. The biosensors have a binding domain and a dye, or a dye which is attached directly to the target of interest. Binding domains contemplated by the invention include biomolecules or fragments of biomolecules that interact with target molecules of interest and can be specific to a given conformational state or covalent modification of the molecule (e.g. phosphorylation). In one embodiment, the binding domain of a biosensor is a single chain variable fragment (scFv) with a dye of the invention linked to a CDR3 region. The invention also provides environmentally sensitive dyes useful for detecting changes in the binding, conformational change, or posttranslational modification of the selected target.
摘要翻译：本发明提供染料，生物传感器和使用染料和生物传感器检测所选择的靶分子的方法。生物传感器具有结合结构域和染料，或直接连接到目标靶的染料。本发明涵盖的结合域包括生物分子的生物分子或与目的靶分子相互作用并且可以对分子的给定构象状态或共价修饰（例如磷酸化）特异性的生物分子。在一个实施方案中，生物传感器的结合结构域是与CDR3区域连接的本发明染料的单链可变片段（scFv）。本发明还提供了用于检测所选靶的结合，构象变化或翻译后修饰的变化的环境敏感染料。

3. 发明授权

US07745377B2 Labeled peptides, proteins and antibodies and processes and intermediates useful for their preparation 失效
标题翻译：标记的肽，蛋白质和抗体以及用于其制备的方法和中间体
公开(公告)号：US07745377B2
公开(公告)日：2010-06-29
申请号：US11122795
申请日：2005-05-05
申请人： Klaus M. Hahn , Alexei Toutchkine , Rajeev Muthyala , Vadim Kraynov , Steven J. Bark , Dennis R. Burton , Chester Chamberlain
发明人： Klaus M. Hahn , Alexei Toutchkine , Rajeev Muthyala , Vadim Kraynov , Steven J. Bark , Dennis R. Burton , Chester Chamberlain
IPC分类号： C40B60/04 , G01N33/543 , C07D277/60 , C07D413/00 , C07D209/00
CPC分类号： C07K1/1077 , C07K1/13
摘要： The invention provides peptide synthons having protected functional groups for attachment of desired moieties (e.g. functional molecules or probes). Also provided are peptide conjugates prepared from such synthons, and synthon and conjugate preparation methods including procedures for identifying the optimum probe attachment site. Biosensors are provided having environmentally sensitive dyes that can locate specific biomolecules within living cells and detect chemical and physiological changes in those biomolecules as the living cell is moving, metabolizing and reacting to its environment. Methods are included for detecting GTP activation of a Rho GTPase protein using polypeptide biosensors. When the biosensor binds GTP-activated Rho GTPase protein, the environmentally sensitive dye emits a signal of a different lifetime, intensity or wavelength than when not bound. New fluorophores whose fluorescence responds to environmental changes are also provided that have improved detection and attachment properties, and that can be used in living cells, or in vitro.
摘要翻译：本发明提供具有用于连接所需部分（例如功能分子或探针）的保护的官能团的肽合成子。还提供了由这种合成子制备的肽缀合物，以及合成子和共轭物制备方法，包括用于鉴定最佳探针附着位点的程序。提供具有环境敏感染料的生物传感器，其可以在活细胞内定位特定的生物分子，并且当活细胞移动，代谢和对其环境作出反应时，检测那些生物分子中的化学和生理变化。包括使用多肽生物传感器检测Rho GTPase蛋白的GTP活化的方法。当生物传感器结合GTP激活的Rho GTPase蛋白时，环境敏感的染料会发出与不结合不同的寿命，强度或波长的信号。还提供了荧光对环境变化的响应的新荧光团，其具有改进的检测和附着性质，并且可用于活细胞或体外。

4. 发明授权

US07351797B1 Labeled peptides, and processes and intermediates useful for their preparation 失效
标题翻译：标记的肽，以及可用于其制备的方法和中间体
公开(公告)号：US07351797B1
公开(公告)日：2008-04-01
申请号：US10381903
申请日：2000-09-29
申请人： Klaus M. Hahn , Steven J. Bark
发明人： Klaus M. Hahn , Steven J. Bark
IPC分类号： C07K14/00 , A61K39/395
CPC分类号： C07K1/13 , C07K1/1077 , C07K7/08 , Y02P20/55
摘要： The invention provides intermediates and methods that allow for site-specific modification of peptides after synthesis. Accordingly, functional molecules can be selectively linked to a peptide to provide a peptide conjugate having altered biological, chemical, or physical properties. For example, functional molecules (e.g. biophysical probes, peptides, polynucleotides, and therapeutic agents) can be linked to a peptide to provide a peptide conjugate having differing and useful properties. The invention also provides a compound of formula (III): wherein: R6 is a peptide; X is a direct bond or a linking group; R7 is hydrogen, (C1-C6)alkyl, an amino protecting group, or a radical comprising one or more aminooxy groups; Y is a direct bond or a linking group; and D is a functional molecule.
摘要翻译：本发明提供允许合成后肽的位点特异性修饰的中间体和方法。因此，功能分子可以选择性地连接到肽以提供具有改变的生物学，化学或物理性质的肽缀合物。例如，功能分子（例如生物物理探针，肽，多核苷酸和治疗剂）可以连接到肽以提供具有不同和有用性质的肽缀合物。本发明还提供式（III）化合物：其中：R 6是肽; X是直接键或连接基团; R 7是氢，（C 1 -C 6 -C 6）烷基，氨基保护基或包含一个或多个氨基氧基的基团; Y是直接键或连接基团; D是功能性分子。

5. 发明授权

US07176037B2 Labeled peptides, proteins and antibodies and processes and intermediates useful for their preparation 失效
标题翻译：标记的肽，蛋白质和抗体以及用于其制备的方法和中间体
公开(公告)号：US07176037B2
公开(公告)日：2007-02-13
申请号：US10455713
申请日：2003-06-03
申请人： Klaus M. Hahn , Alexei Toutchkine , Rajeev Muthyala , Vadim Kraynov , Steven J. Bark , Dennis R. Burton , Chester Chamberlain
发明人： Klaus M. Hahn , Alexei Toutchkine , Rajeev Muthyala , Vadim Kraynov , Steven J. Bark , Dennis R. Burton , Chester Chamberlain
IPC分类号： G01N33/533 , G01N33/532 , G01N21/76 , G01N33/53 , C07K1/13 , C07D277/62
CPC分类号： C07K1/13 , C07K1/1077
摘要： The invention provides peptide synthons having protected functional groups for attachment of desired moieties (e.g. functional molecules or probes). Also provided are peptide conjugates prepared from such synthons, and synthon and conjugate preparation methods including procedures for identifying optimum probe attachment sites. Biosensors are provided having functional molecules that can locate and bind to specific biomolecules within living cells. Biosensors can detect chemical and physiological changes in those biomolecules as living cells are moving, metabolizing and reacting to its environment. Methods are included for detecting GTP activation of a Rho GTPase protein using polypeptide biosensors. When the biosensor binds GTP-activated Rho GTPase protein, an environmentally sensitive dye emits a signal of a different lifetime, intensity or wavelength than when not bound. New fluorophores whose fluorescence responds to environmental changes are also provided that have improved detection and attachment properties, and that can be used in living cells, or in vitro.
摘要翻译：本发明提供具有用于连接所需部分（例如功能分子或探针）的保护的官能团的肽合成子。还提供了由这种合成子制备的肽缀合物，以及合成子和缀合物制备方法，包括鉴定最佳探针附着位点的程序。生物传感器具有能够定位并结合活细胞内的特定生物分子的功能分子。生物传感器可以检测生物分子中的化学和生理变化，因为活细胞正在移动，代谢并对其环境作出反应。包括使用多肽生物传感器检测Rho GTPase蛋白的GTP活化的方法。当生物传感器结合GTP激活的Rho GTPase蛋白质时，环境敏感的染料会发出与未结合不同的寿命，强度或波长的信号。还提供了荧光对环境变化的响应的新荧光团，其具有改进的检测和附着性质，并且可用于活细胞或体外。

6. 发明授权

US06951947B2 Labeled peptides, proteins and antibodies and processes and intermediates useful for their preparation 失效
标题翻译：标记的肽，蛋白质和抗体以及用于其制备的方法和中间体
公开(公告)号：US06951947B2
公开(公告)日：2005-10-04
申请号：US09839577
申请日：2001-04-20
申请人： Klaus M. Hahn , Alexei Toutchkine
发明人： Klaus M. Hahn , Alexei Toutchkine
IPC分类号： C07K1/107 , C07K1/13 , C07D277/62 , C07D263/52
CPC分类号： C07K1/1077 , C07K1/13
摘要： The invention provides peptide synthons having protected functional groups for attachment of desired moieties (e.g. functional molecules or probes). Also provided are peptide conjugates prepared from such synthons, and synthon and conjugate preparation methods including procedures for identifying the optimum probe attachment site. Biosensors are provided having environmentally sensitive dyes that can locate specific biomolecules within living cells and detect chemical and physiological changes in those biomolecules as the living cell is moving, metabolizing and reacting to its environment. Methods are included for detecting GTP activation of a Rho GTPase protein using polypeptide biosensors. When the biosensor binds GTP-activated Rho GTPase protein, the environmentally sensitive dye emits a signal of a different lifetime, intensity or wavelength than when not bound. New fluorophores whose fluorescence responds to environmental changes are also provided that have improved detection and attachment properties, and that can be used in living cells, or in vitro.
摘要翻译：本发明提供具有用于连接所需部分（例如功能分子或探针）的保护的官能团的肽合成子。还提供了由这种合成子制备的肽缀合物，以及合成子和共轭物制备方法，包括用于鉴定最佳探针附着位点的程序。提供具有环境敏感染料的生物传感器，其可以在活细胞内定位特定的生物分子，并且当活细胞移动，代谢和对其环境作出反应时，检测那些生物分子中的化学和生理变化。包括使用多肽生物传感器检测Rho GTPase蛋白的GTP活化的方法。当生物传感器结合GTP激活的Rho GTPase蛋白时，环境敏感的染料会发出与不结合不同的寿命，强度或波长的信号。还提供了荧光对环境变化的响应的新荧光团，其具有改进的检测和附着性质，并且可用于活细胞或体外。

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