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    • 1. 发明申请
    • FUSION PROTEINS
    • 融合蛋白
    • US20130189238A1
    • 2013-07-25
    • US13774587
    • 2013-02-22
    • Syntaxin Ltd.Allergan Inc.
    • Keith FOSTERJohn CHADDOCKPhilip MARKSPatrick STANCOMBEKei Roger AOKIJoseph FRANCISLance STEWARD
    • C12N9/96
    • C12N9/96A61K38/00A61K47/64C07K2319/01C07K2319/33C07K2319/50C12N9/50
    • A single chain, polypeptide fusion protein, comprising: a non-cytotoxic protease, or a fragment thereof, which protease or protease fragment is capable of cleaving a protein of the exocytic fusion apparatus of a nociceptive sensory afferent; a dynorphin Targeting Moiety that is capable of binding to a Binding Site on the nociceptive sensory afferent, which Binding Site is capable of undergoing endocytosis to be incorporated into an endosome within the nociceptive sensory afferent; a protease cleavage site at which site the fusion protein is cleavable by a protease, wherein the protease cleavage site is located between the non-cytotoxic protease or fragment thereof and the dynorphin Targeting Moiety; and a translocation domain that is capable of translocating the protease or protease fragment from within an endosome, across the endosomal membrane and into the cytosol of the nociceptive sensory afferent. Nucleic acid sequences encoding the polypeptide fusion proteins, methods of preparing same and uses thereof are also described.
    • 一种单链多肽融合蛋白,其包含:非细胞毒性蛋白酶或其片段,所述蛋白酶或蛋白酶片段能够切割伤害性感觉传入的胞外融合装置的蛋白质; 能够结合伤害性感觉传入的结合位点的强啡肽靶向部位,该结合位点能够经历内吞作用以掺入伤害性感觉传入内的内体; 蛋白酶切割位点位于融合蛋白可被蛋白酶切割的蛋白酶切割位点,其中蛋白酶切割位点位于非细胞毒性蛋白酶或其片段与强啡肽靶向部位之间; 以及易位区域,其能够将位于内体内的蛋白酶或蛋白酶片段穿过内体膜并转移到伤害性感觉传入物的胞质溶胶中。 还描述了编码多肽融合蛋白的核酸序列,其制备方法及其用途。