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    Lipid matrix-assisted chemical ligation and synthesis of membrane polypeptides
    2.
    发明授权
    Lipid matrix-assisted chemical ligation and synthesis of membrane polypeptides 有权
    脂质基质辅助化学连接和膜多肽的合成

    公开(公告)号：US06451543B1

    公开(公告)日：2002-09-17

    申请号：US09384302

    申请日：1999-08-26

    申请人： Gerd. G. Kochendoerfer ,  Christie L. Hunter ,  Stephen B. H. Kent ,  Paolo Botti

    发明人： Gerd. G. Kochendoerfer ,  Christie L. Hunter ,  Stephen B. H. Kent ,  Paolo Botti

    IPC分类号： G01N3353

    CPC分类号： A61K49/0056 ,  A61K49/0041 ,  C07C229/16 ,  C07K1/023 ,  C07K1/026 ,  C07K1/04 ,  C07K1/042 ,  C07K1/045 ,  C07K14/005 ,  C07K14/215 ,  C07K14/36 ,  C07K14/43522 ,  C07K14/5421 ,  C07K14/705 ,  C07K2319/00 ,  C12N2740/16322 ,  C12N2760/16022 ,  Y10S435/87

    摘要： The present invention relates to methods and compositions for lipid matrix-assisted chemical ligation and synthesis of membrane polypeptides that are incorporated in a lipid matrix. The invention is exemplified in production of a prefolded membrane polypeptide embedded within a lipid matrix via stepwise chemoselective chemical ligation of unprotected peptide segments, where at least one peptide segment is embedded in a lipid matrix. Any chemoselective reaction chemistry amenable for ligation of unprotected peptide segments can be employed. Suitable lipid matrices include liposomes, micelles, cell membrane patches and optically isotropic cubic lipidic phase matrices. Prefolded synthetic and semi-synthetic membrane polypeptides synthesized according to the methods and compositions of the invention also permit site-specific incorporation of one or more detectable moieties, such as a chromophore, which can be conveniently introduced during synthesis. The methods and compositions of the invention have multiple uses. For example, they can be used to assay ligand binding to membrane polypeptides and domains comprising a receptor, and thus are extremely useful for structure/function studies, drug screening/selection/design, and diagnostics and the like, including high-throughput applications. The methods and compositions of the invention are particularly suited for FRET analyses of previously inaccessible membrane polypeptides.

    摘要翻译： 本发明涉及掺入脂质基质中的脂质基质辅助化学连接和膜多肽的合成的方法和组合物。 本发明通过逐步化学选择性化学连接未受保护的肽段（其中至少一个肽片段嵌入脂质基质）生产嵌入脂质基质内的预折叠膜多肽。 可以使用适用于未保护肽段连接的任何化学选择性反应化学物质。 合适的脂质基质包括脂质体，胶束，细胞膜片和光学各向同性立体脂质相基质。 根据本发明的方法和组合物合成的预先折叠的合成和半合成膜多肽还允许位点特异性引入一个或多个可检测部分，例如发色团，其可以在合成期间方便地引入。 本发明的方法和组合物具有多种用途。 例如，它们可用于测定配体结合膜多肽和包含受体的结构域，因此对于结构/功能研究，药物筛选/选择/设计和诊断等（包括高通量应用）非常有用。 本发明的方法和组合物特别适用于以前不可接近的膜多肽的FRET分析。

    Compositions for lipid matrix-assisted chemical ligation
    3.
    发明授权
    Compositions for lipid matrix-assisted chemical ligation 失效
    用于脂质基质辅助化学连接的组合物

    公开(公告)号：US07482425B2

    公开(公告)日：2009-01-27

    申请号：US10207330

    申请日：2002-07-30

    申请人： Gerd. G. Kochendoerfer ,  Christie L. Hunter ,  Stephen B. H. Kent ,  Paolo Botti

    发明人： Gerd. G. Kochendoerfer ,  Christie L. Hunter ,  Stephen B. H. Kent ,  Paolo Botti

    IPC分类号： A61K38/00

    CPC分类号： C07K14/005 ,  C07K1/023 ,  C07K1/026 ,  C07K1/04 ,  C07K1/042 ,  C07K14/215 ,  C07K14/245 ,  C07K14/36 ,  C07K14/43522 ,  C07K14/5421 ,  C07K14/705 ,  C07K2319/00 ,  C12N2740/16322 ,  C12N2760/16022

    摘要： The present invention relates to methods and compositions for lipid matrix-assisted chemical ligation and synthesis of membrane polypeptides that are incorporated in a lipid matrix. The invention is exemplified in production of a prefolded membrane polypeptide embedded within a lipid matrix via stepwise chemoselective chemical ligation of unprotected peptide segments, where at least one peptide segment is embedded in a lipid matrix. Any chemoselective reaction chemistry amenable for ligation of unprotected peptide segments can be employed. Suitable lipid matrices include liposomes, micelles, cell membrane patches and optically isotropic cubic lipidic phase matrices. Prefolded synthetic and semi-synthetic membrane polypeptides synthesized according to the methods and compositions of the invention also permit site-specific incorporation of one or more detectable moieties, such as a chromophore, which can be conveniently introduced during synthesis. The methods and compositions of the invention have multiple uses. For example, they can be used to assay ligand binding to membrane polypeptides and domains comprising a receptor, and thus are extremely useful for structure/function studies, drug screening/selection/design, and diagnostics and the like, including high-throughput applications. The methods and compositions of the invention are particularly suited for FRET analyses of previously inaccessible membrane polypeptides.

    摘要翻译： 本发明涉及掺入脂质基质中的脂质基质辅助化学连接和膜多肽的合成的方法和组合物。 本发明通过逐步化学选择性化学连接未受保护的肽段（其中至少一个肽片段嵌入脂质基质）生产嵌入脂质基质内的预折叠膜多肽。 可以使用适用于未保护肽段连接的任何化学选择性反应化学物质。 合适的脂质基质包括脂质体，胶束，细胞膜片和光学各向同性立体脂质相基质。 根据本发明的方法和组合物合成的预先折叠的合成和半合成膜多肽还允许位点特异性引入一个或多个可检测部分，例如发色团，其可以在合成期间方便地引入。 本发明的方法和组合物具有多种用途。 例如，它们可用于测定配体结合膜多肽和包含受体的结构域，因此对于结构/功能研究，药物筛选/选择/设计和诊断等（包括高通量应用）非常有用。 本发明的方法和组合物特别适用于以前不可接近的膜多肽的FRET分析。