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    Vm23 and Vm24, two scorpion peptides that block human T-lymphocyte potassium channels (sub-type Kv1.3) with high selectivity and decrease the in vivo DTH-responses in rats
    2.
    发明授权
    Vm23 and Vm24, two scorpion peptides that block human T-lymphocyte potassium channels (sub-type Kv1.3) with high selectivity and decrease the in vivo DTH-responses in rats 有权
    Vm23和Vm24，两种蝎子肽以高选择性阻断人类T淋巴细胞钾通道（亚型Kv1.3），降低大鼠体内DTH反应

    公开(公告)号：US08394770B2

    公开(公告)日：2013-03-12

    申请号：US12599978

    申请日：2007-05-14

    申请人： Lourival Domingos Possani-Postay ,  Georgina Gurrola-Briones ,  Saida Patricia Salas-Castillo ,  César Vicente Ferreira Batista ,  Zoltán S. Varga ,  György Panyi ,  Rezsö Gáspár

    发明人： Lourival Domingos Possani-Postay ,  Georgina Gurrola-Briones ,  Saida Patricia Salas-Castillo ,  César Vicente Ferreira Batista ,  Zoltán S. Varga ,  György Panyi ,  Rezsö Gáspár

    IPC分类号： A61K38/16 ,  C07K14/435

    CPC分类号： C07K14/43522 ,  A61K38/00 ,  G01N33/505 ,  G01N33/564 ,  G01N33/6872 ,  G01N33/6893 ,  G01N33/9493 ,  G01N2500/00 ,  G01N2800/245

    摘要： Potassium channels Kv1.3 are known to be implicated in immunological diseases and graft rejections. Disclosed are peptides capable of blocking with high affinity and specificity potassium channels Kv1.3, their pharmaceutical compositions, and methods for their use to block Kv1.3 potassium channels, to treat various immunological conditions and to diagnostic applications. Methods for their chemical synthesis and correct folding are also disclosed. Exemplary peptides correspond to protein components (Vm23 and Vm24) isolated from the venom of the Mexican scorpion Vaejovis mexicanus smithi. Vm23 and Vm24 bind to hKv1.3 channels in an almost irreversible manner, showing a Kd value in the order of 3 picomolar range, when applied to human lymphocytes cultures in vitro. Vm24 was chemically synthesized and used in in vivo experiments to successfully treat sensitized rats (on the DTH-response). Neither Vm24 nor synthetic Vm24 is toxic to mice when injected at relatively high concentrations (assayed up to 10,000 micrograms per kilogram mouse body weight). These peptides (Vm24 and Vm23) and their functional equivalent analogs with at least 83% of sequence identity are lead compounds, candidates for the treatment of various immunological conditions and diagnostic applications.

    摘要翻译： 已知钾通道Kv1.3涉及免疫疾病和移植排斥。 公开了能够以高亲和力和特异性的钾通道Kv1.3，其药物组合物及其用于阻断Kv1.3K3通道的方法，以治疗各种免疫条件和诊断应用的肽。 还公开了它们的化学合成和正确折叠的方法。 示例性肽对应于从墨西哥蝎子Vaejovis mexicanus smithi的毒液分离的蛋白质组分（Vm23和Vm24）。 Vm23和Vm24以几乎不可逆的方式结合hKv1.3通道，当体外应用于人类淋巴细胞培养物时，显示出3皮摩尔范围的Kd值。 Vm24化学合成并用于体内实验以成功治疗致敏大鼠（DTH反应）。 当以相对高的浓度注射时，Vm24和合成的Vm24都不对小鼠有毒（测定每千克小鼠体重达10,000微克）。 具有至少83％序列同一性的这些肽（Vm24和Vm23）及其功能等同类似物是铅化合物，用于治疗各种免疫条件和诊断应用的候选物。