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22 条记录 (耗时 0.026 秒)

    Inhibitors of prion formation
    4.
    发明授权
    Inhibitors of prion formation 失效
    抑制朊蛋白形成

    公开(公告)号：US06365359B1

    公开(公告)日：2002-04-02

    申请号：US09439921

    申请日：1999-11-12

    申请人： Stanley B. Prusiner ,  Fred E. Cohen ,  Thomas L. James ,  Kiyotoshi Kaneko

    发明人： Stanley B. Prusiner ,  Fred E. Cohen ,  Thomas L. James ,  Kiyotoshi Kaneko

    IPC分类号： G01N3353

    CPC分类号： A61K31/417 ,  A61K31/4178 ,  A61K31/7048 ,  A61K31/7076 ,  A61K38/00 ,  C07H21/00 ,  C07K1/045 ,  C07K1/047 ,  C07K14/47 ,  Y02P20/582

    摘要： Molecules are disclosed that interact with the cellular components involved in conversion of PrPC to PrPSc. The molecules disclosed can be small molecules, peptides or protein analogs, e.g. analogs of PrPC. In one embodiment, these molecules interfere with prion formation and/or replication, e.g. by preventing interactions of proteins involved in a prion complex or by interfering with &bgr;-sheet formation. In another embodiment, the molecules of the invention promote PrPC conversion to PrPSc, e.g. by binding to PrPC and facilitating a conformational change from PrPC to PrPSc.

    摘要翻译： 公开了与涉及PrPC转化为PrPSc的细胞成分相互作用的分子。 所公开的分子可以是小分子，肽或蛋白质类似物，例如 PrPC类似物。 在一个实施方案中，这些分子干扰朊病毒形成和/或复制，例如。 通过防止参与朊病毒复合物的蛋白质的相互作用或干扰β片段的形成。 在另一个实施方案中，本发明的分子促进PrPC转化为PrPSc，例如。 通过绑定到PrPC并促进从PrPC到PrPSc的构象变化。

    Soluble form of PrP.sup.SC which is insoluble in native form
    5.
    发明授权
    Soluble form of PrP.sup.SC which is insoluble in native form 失效
    可溶形式的PrPSC，其不溶于天然形式

    公开(公告)号：US5834593A

    公开(公告)日：1998-11-10

    申请号：US740947

    申请日：1996-11-05

    申请人： Stanley B. Prusiner ,  Fred E. Cohen ,  Tamaki Muramoto

    发明人： Stanley B. Prusiner ,  Fred E. Cohen ,  Tamaki Muramoto

    IPC分类号： G01N33/50 ,  A61K38/00 ,  A61K45/00 ,  A61P25/00 ,  A61P25/16 ,  A61P25/28 ,  C07K14/00 ,  C07K14/47 ,  C07K16/18 ,  C12N15/09 ,  G01N33/15 ,  G01N33/53 ,  C07K1/00 ,  C07K16/00 ,  C07K17/00

    CPC分类号： C07K14/00 ,  C07K14/47 ,  C07K16/18 ,  A61K38/00

    摘要： The invention includes deleting codon segments from DNA expressing a native protein (e.g., PrP.sup.Sc) in order to obtain a shorter, soluble protein which mimics characteristics of an insoluble native (e.g., PrP.sup.Sc) protein. Soluble proteins of the invention are characterized by: (1) having less amino acids than the full length native protein; (2) having a higher degree of solubility than the native protein; (3) retaining the basic biological characteristics of the native protein such as (a) not being subject to enzymatic digestion and (b) causing disease. Soluble proteins of the invention are obtained by providing a DNA sequence which encodes a native protein and systematically removing codons, making copies of the shortened versions of DNA which are then expressed to provide the shortened proteins. The shortened proteins are then tested for solubility. Soluble proteins are then further tested to confirm that they retain the biological characteristics of the native protein. The soluble form can also be created by adding amino acids, binding a hydrophilic moiety to the native protein or combinations of deleting, adding, and binding hydrophilic moieties to the protein.

    摘要翻译： 本发明包括从表达天然蛋白质（例如PrPSc）的DNA中删除密码子片段，以获得模拟不溶性天然（例如PrPSc）蛋白质特征的较短的可溶性蛋白质。 本发明的可溶性蛋白质的特征在于：（1）具有比全长天然蛋白质少的氨基酸; （2）具有比天然蛋白质更高的溶解度; （3）保留天然蛋白质的基本生物学特性，如（a）不经酶消化和（b）引起疾病。 通过提供编码天然蛋白质的DNA序列并系统地除去密码子，制备DNA的缩短形式的拷贝，然后进行表达以提供缩短的蛋白质，从而获得本发明的可溶性蛋白质。 然后测试缩短的蛋白质的溶解度。 然后进一步测试可溶性蛋白质以证实它们保留天然蛋白质的生物学特性。 可溶性形式也可以通过加入氨基酸，将亲水部分结合到天然蛋白质或者将蛋白质的缺失，添加和结合亲水部分的组合来产生。

    Nucleic acid encoding prion protein variant
    8.
    发明授权
    Nucleic acid encoding prion protein variant 失效
    编码朊病毒蛋白变体的核酸

    公开(公告)号：US5962669A

    公开(公告)日：1999-10-05

    申请号：US868162

    申请日：1997-06-02

    申请人： Stanley B. Prusiner ,  Fred E. Cohen ,  Thomas L. James ,  Kiyotoshi Kaneko

    发明人： Stanley B. Prusiner ,  Fred E. Cohen ,  Thomas L. James ,  Kiyotoshi Kaneko

    IPC分类号： A61K31/417 ,  A61K31/4178 ,  A61K38/00 ,  C07H21/00 ,  C07K1/04 ,  C07K14/47 ,  C12N15/11

    CPC分类号： A61K31/7048 ,  A61K31/417 ,  A61K31/4178 ,  A61K31/7076 ,  C07H21/00 ,  C07K1/045 ,  C07K1/047 ,  C07K14/47 ,  A61K38/00 ,  Y02P20/582

    摘要： A protein designated Prion Protein Modulator Factor (PPMF) is disclosed which protein is an auxiliary factor in prion replication. PPMF is primarily characterized by its ability to bind to PrP.sup.C and facilitate a conformational change from PrP.sup.C to PrP.sup.Sc. A discontinuous epitope on PrP.sup.C comprising residues 172, 215 and 219 of human PrP.sup.C binds PPMF which is encoded by a nucleotide sequence derived from an organism selected from the group consisting of cow, sheep, mouse, hamster and human. In converting PrP.sup.C to PrP.sup.Sc the PPMF forms a PrP.sup.C /PrP.sup.Sc complex and is a rate limiting compound in the formation of that complex. Molecules, including antibodies, which bind PPMF or its epitope on PrP.sup.C are useful in the treatment of prion disease. Pharmacophores of the PrP.sup.C epitope are disclosed as are useful therapeutics and pharmacophores of the PPMF surface which binds PrP.sup.C. Animals resistant to prion disease are taught as are genes for producing such animals. Assay systems are disclosed which use PPMF to amplify PrP.sup.Sc is a sample being tested.

    摘要翻译： 公开了一种称为朊病毒蛋白调节因子（PPMF）的蛋白质，其中蛋白质是朊病毒复制中的辅助因子。 PPMF的主要特征在于其能够结合PrPC并促进从PrPC到PrPSc的构象变化。 PrPC上包含人PrPC残基172,215和219的不连续表位结合PPMF，其由源自选自牛，绵羊，小鼠，仓鼠和人的生物体的核苷酸序列编码。 在将PrPC转化为PrPSc时，PPMF形成PrPC / PrPSc复合物，并且是形成复合物的速率限制化合物。 结合PPMF或其PrPC上的表位的分子，包括抗体，可用于治疗朊病毒疾病。 公开了PrPC表位的药代号，作为结合PrPC的PPMF表面的有用治疗剂和药效团。 具有抗朊病毒抗性的动物被教导为用于生产这种动物的基因。 公开了使用PPMF来扩增PrPSc的测定系统是正在测试的样品。