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39 条记录 (耗时 0.026 秒)

    Surrogates of post-translationally modified proteins and uses thereof
    4.
    发明授权
    Surrogates of post-translationally modified proteins and uses thereof 有权
    翻译后修饰蛋白质的替代物及其用途

    公开(公告)号：US09417248B2

    公开(公告)日：2016-08-16

    申请号：US13984423

    申请日：2012-02-10

    申请人： Michael Chorev ,  Jose A. Halperin

    发明人： Michael Chorev ,  Jose A. Halperin

    IPC分类号： G01N33/68 ,  C07K16/28 ,  C07K14/705 ,  C07K16/44 ,  G01N33/564

    CPC分类号： G01N33/6893 ,  C07K14/70596 ,  C07K16/2896 ,  C07K16/44 ,  G01N33/564 ,  G01N33/6872 ,  G01N2333/70596 ,  G01N2440/00 ,  G01N2440/38 ,  G01N2800/042

    摘要： 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.

    摘要翻译： 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，其难以以均匀形式获得，并且以免疫和使用所需的量作为方便的标准品，校准物和/或参考化合物获得，其有助于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。

    Phenylethylamine derivatives
    9.
    发明授权
    Phenylethylamine derivatives 失效
    苯乙胺衍生物

    公开(公告)号：US06251938B1

    公开(公告)日：2001-06-26

    申请号：US09335555

    申请日：1999-06-18

    申请人： Michael Chorev ,  Tamar Goren ,  Yacov Herzig ,  Jeffrey Sterling ,  Marta Weinstock-Rosin ,  Moussa B. H. Youdim

    发明人： Michael Chorev ,  Tamar Goren ,  Yacov Herzig ,  Jeffrey Sterling ,  Marta Weinstock-Rosin ,  Moussa B. H. Youdim

    IPC分类号： A61K3127

    CPC分类号： C07C271/42 ,  C07C271/56

    摘要： This invention is directed to compounds of the following formula: wherein m is from 0-4; X is O or S; Y is halogeno; R1 is hydrogen or C1-4 alkyl; R2 is hydrogen, C1-4 alkyl or optionally substituted propargyl; and R3 and R4 are each independently hydrogen, C1-8 alkyl, C6-12 aryl, C6-12 cycloalkyl or C6-12 aralkyl, R5 is hydrogen or C1-4 alkyl; and pharmaceutically acceptable salts thereof, provided that when X is O, R2 is optionally substituted propargyl. This invention is also directed to the use of these compounds for treating depression, Attention Deficit Disorder (ADD), Attention Deficit and Hyperactivity Disorder (ADHD), Tourette's Syndrome, Alzheimer's Disease and other dementia's such as senile dementia, dementia of the Parkinson's type, vascular dementia and Lewy body dementia. This invention is further directed to a pharmaceutical composition comprising a therapeutically effective amount of the above-defined compounds and a pharmaceutically acceptable carrier.

    摘要翻译： 本发明涉及下式的化合物：其中m为0-4; X是O或S; Y为卤素; R1是氢或C1-4烷基; R2是氢，C1-4烷基或任选取代的炔丙基; 并且R 3和R 4各自独立地为氢，C 1-8烷基，C 6-12芳基，C 6-12环烷基或C 6-12芳烷基，R 5为氢或C 1-4烷基; 其中X为O时，R2为任选取代的炔丙基。本发明还涉及这些化合物用于治疗抑郁症，注意力缺陷症（ADD），注意力缺陷和多动症（ADHD）的用途， Tourette综合征，阿尔茨海默病和其他痴呆症如老年性痴呆，帕金森氏型痴呆，血管性痴呆和路易体痴呆。本发明还涉及一种药物组合物，其包含治疗有效量的上述化合物和药学上可接受的 载体