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    • 1. 发明申请
      WO2012109538A3 SURROGATES OF POST-TRANSLATIONALLY MODIFIED PROTEINS AND USES THEREOF 审中-公开
    • SURROGATES OF POST-TRANSLATIONALLY MODIFIED PROTEINS AND USES THEREOF
    • 翻译后修饰蛋白质的现象及其用途
    • WO2012109538A3
    • 2012-11-22
    • PCT/US2012024645
    • 2012-02-10
    • HARVARD COLLEGE , CHOREV MICHAEL , HALPERIN JOSE A
    • CHOREV MICHAEL , HALPERIN JOSE A
    • C07K14/435 , C07K16/18 , G01N33/533 , G01N33/574
    • G01N33/6893 , C07K14/70596 , C07K16/2896 , C07K16/44 , G01N33/564 , G01N33/6872 , G01N2333/70596 , G01N2440/00 , G01N2440/38 , G01N2800/042
    • The present invention provides compounds that are surrogates of post-translationally modified proteins and uses thereof. Numerous diseases are associated with post- translationally modified proteins that are difficult to obtain in homogenous form and in quantities needed for immunization and use as convenient standards, calibrators, and/or reference compounds that facilitate the detection and analysis of endogenous post- translationally modified proteins. The surrogate compounds of the invention typically comprise antigenic epitopes (one of which carries a post-translational modification) that are tethered by a flexible and hydrophilic linker. The resulting compound behaves like a surrogate of the post-translationally modified protein because it preserves the character of the included antigens and allows recognition by specific antibodies targeting the individual antigens. The surrogate compounds may be prepared by covalently joining two or more polypeptide epitopes using one or more linkers, wherein at least one of the epitopes comprises a post-translational modification. In one aspect, the surrogate compounds of the invention comprise a C-terminal epitope and a glycated epitope of human CD59. The inventive methods allow quantification of the levels of glycated CD59 in the serum in human subjects, particularly those with diabetes or pre-diabetes. This technological platform of post-translationally modified protein surrogates can be applied to other diseases associated with post-translationally modified proteins (e.g., autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus). In another aspect, the invention provides antibodies that bind specifically to the compounds of the invention and methods for producing such antibodies.
    • 本发明提供了作为翻译后修饰的蛋白质的替代物的化合物及其用途。 许多疾病与翻译后修饰的蛋白质相关联，其难以以均匀的形式获得，并且以免疫和使用所需的量作为方便的标准品，校准物和/或参考化合物，促进内源性翻译后修饰的蛋白质的检测和分析 。 本发明的替代化合物通常包含被柔性和亲水接头连接的抗原表位（其中一个携带翻译后修饰）。 所得化合物表现为翻译后修饰的蛋白质的替代物，因为其保留所包含的抗原的特征，并允许通过针对各个抗原的特异性抗体进行识别。 替代化合物可以通过使用一种或多种接头共价连接两个或多个多肽表位来制备，其中至少一个表位包含翻译后修饰。 一方面，本发明的替代化合物包含人CD59的C-末端表位和糖基化表位。 本发明的方法允许定量人受试者，特别是糖尿病或前期糖尿病患者血清中糖基化CD59的水平。 翻译后修饰的蛋白质替代物的这种技术平台可以应用于与翻译后修饰的蛋白质（例如自身免疫性疾病如多发性硬化症，类风湿性关节炎和系统性红斑狼疮）相关的其它疾病。 另一方面，本发明提供了与本发明化合物特异性结合的抗体以及用于产生此类抗体的方法。
    • 基本信息 添加关注 加入工作空间 PDF全文 PDF下载 全文下载 相似专利 双屏查看 权利要求书 说明书全文 Global Dossier Espacenet 法律信息 同族专利 专利引用
    • 4. 发明申请
      WO2012109538A8 SURROGATES OF POST-TRANSLATIONALLY MODIFIED PROTEINS AND USES THEREOF 审中-公开
    • SURROGATES OF POST-TRANSLATIONALLY MODIFIED PROTEINS AND USES THEREOF
    • 翻译后修饰的蛋白质的去除剂及其用途
    • WO2012109538A8
    • 2012-10-04
    • PCT/US2012024645
    • 2012-02-10
    • HARVARD COLLEGE , CHOREV MICHAEL , HALPERIN JOSE A
    • CHOREV MICHAEL , HALPERIN JOSE A
    • C07K14/435 , C07K16/18 , G01N33/533 , G01N33/574
    • G01N33/6893 , C07K14/70596 , C07K16/2896 , C07K16/44 , G01N33/564 , G01N33/6872 , G01N2333/70596 , G01N2440/00 , G01N2440/38 , G01N2800/042
    • The present invention provides compounds that are surrogates of post-translationally modified proteins and uses thereof. Numerous diseases are associated with post- translationally modified proteins that are difficult to obtain in homogenous form and in quantities needed for immunization and use as convenient standards, calibrators, and/or reference compounds that facilitate the detection and analysis of endogenous post- translationally modified proteins. The surrogate compounds of the invention typically comprise antigenic epitopes (one of which carries a post-translational modification) that are tethered by a flexible and hydrophilic linker. The resulting compound behaves like a surrogate of the post-translationally modified protein because it preserves the character of the included antigens and allows recognition by specific antibodies targeting the individual antigens. The surrogate compounds may be prepared by covalently joining two or more polypeptide epitopes using one or more linkers, wherein at least one of the epitopes comprises a post-translational modification. In one aspect, the surrogate compounds of the invention comprise a C-terminal epitope and a glycated epitope of human CD59. The inventive methods allow quantification of the levels of glycated CD59 in the serum in human subjects, particularly those with diabetes or pre-diabetes. This technological platform of post-translationally modified protein surrogates can be applied to other diseases associated with post-translationally modified proteins (e.g., autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus). In another aspect, the invention provides antibodies that bind specifically to the compounds of the invention and methods for producing such antibodies.
    • 本发明提供了翻译后修饰蛋白替代物的化合物及其用途。 许多疾病与翻译后修饰的蛋白质相关，所述蛋白质难以以均匀形式和免疫所需的量获得，并且用作便利检测和分析内源性翻译后修饰的蛋白质的便利标准物，校准物和/或参考化合物 。 本发明的替代化合物通常包含通过柔性和亲水性连接子连接的抗原表位（其中一个携带翻译后修饰）。 生成的化合物表现得像翻译后修饰的蛋白质的替代物，因为它保留了包含的抗原的特征并且允许通过靶向单个抗原的特异性抗体识别。 替代化合物可以通过使用一个或多个接头共价连接两个或更多个多肽表位来制备，其中至少一个表位包含翻译后修饰。 在一个方面，本发明的替代化合物包含人CD59的C端表位和糖化表位。 本发明的方法可以量化人受试者血清中糖化CD59的水平，特别是那些患有糖尿病或糖尿病前期的人。 翻译后修饰的蛋白质替代物的这种技术平台可以应用于与翻译后修饰的蛋白质（例如，自身免疫性疾病，例如多发性硬化症，类风湿性关节炎和系统性红斑狼疮）相关的其他疾病。 另一方面，本发明提供了与本发明化合物特异性结合的抗体和生产这种抗体的方法。
    • 基本信息 添加关注 加入工作空间 PDF全文 PDF下载 全文下载 相似专利 双屏查看 权利要求书 说明书全文 Global Dossier Espacenet 法律信息 同族专利 专利引用
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