NOVEL CYCLOPHILINS, ASSOCIATING PROTEINS AND USES
    22.
    发明公开
    NOVEL CYCLOPHILINS, ASSOCIATING PROTEINS AND USES 失效
    新型环磷酰胺,相关蛋白和用途

    公开(公告)号:EP0650522A1

    公开(公告)日:1995-05-03

    申请号:EP92917866.0

    申请日:1992-08-05

    摘要: The cloning and characterization of a new binding protein class, cyclophilin C (cyp C) and homologous proteins, is provided which is capable of binding to, e.g., the immunosuppressive drug cyclosporin A (CsA). The pattern of cyp C mRNA expression differs from that of cyp A mRNA expression, with cyp C being expressed in a more restricted subset of tissues, including those tissues reported to be most affected by CsA therapy. A fusion protein containing, e.g., amino acids 16-212 of cyp C has peptidyl-prolyl-isomerase activity (PPIase), and CsA inhibits this activity. Most significantly, these cyp C fusion proteins can be used as ligands for the identification of intracellular proteins which together form high affinity associations. For example, the cyp C fusion protein binds specifically to a protein of 77 Kd in the absence of CsA, while in the presence of CsA it no longer binds to this p77, but instead binds specifically to a protein 55 Kd, identified as calcineurin (see U.S.S.N. 07/740,175, incorporated herein by reference).

    摘要翻译: 提供了能够结合例如免疫抑制药物环孢菌素A(CsA)的新的结合蛋白类别,亲环蛋白C(cyp C)和同源蛋白的克隆和表征。 cyp C mRNA表达的模式不同于cyp A mRNA表达的模式,其中cyp C在更加限制的组织中表达,包括据报道受CsA治疗影响最大的那些组织。 含有例如cyp C的氨基酸16-212的融合蛋白具有肽基脯氨酰异构酶活性(PPI酶),并且CsA抑制该活性。 最显着的是,这些cyp C融合蛋白可以作为配体用于鉴定一起形成高亲和力关联的细胞内蛋白质。 例如,在不存在CsA的情况下,cyp C融合蛋白与77Kd的蛋白质特异性结合,而在CsA存在下,它不再与该p77结合,而是特异性结合蛋白质55Kd,被鉴定为钙调磷酸酶 参见通过引用并入本文的USSN 07 / 740,175)。