Minimized Streptokinase

描述(由申请人提供)：我们建议创建一个最小化和 与已知的相比具有更好的性能的修饰的链激酶 纤溶酶原激活剂目前用于溶栓治疗。新方法 由Kairos开发，用于蛋白质最小化和高通量筛选 酶变异体将被用来寻找天然蛋白质的较小版本 对含有纤维蛋白的凝块有最大的活性。最小化的 链激酶(MSK)将被设计成：(1)增加对 纤维蛋白；(2)增强了对纤溶酶和其他酶降解的抵抗力； (3)抗抑制剂；(4)热稳定性；(5)低产 成本。此外，最低限度的细菌蛋白质提供了潜在的好处。 抗原性降低。如果成功，一种最小化和优化的链激酶 将为溶栓治疗提供一种新的生物替代药物 据估计，这一市场的年销售额超过2亿美元。 链激酶的成功修饰也将为 设计其他治疗性蛋白质。

DESCRIPTION (provided by applicant): We propose to create a minimized and modified streptokinase having improved properties relative to the known plasminogen activators currently used in thrombolytic therapy. New methods developed by KAIROS for protein minimization and high-throughput screening of enzyme variants wili be used to find smaller versions of the native protein that have maximal activity on fibrin-containing clots. The minimized streptokinase (mSK) will be designed to have: (1 ) increased specificity for fibrin; (2) increased resistance to degradation by plasmin and other proteases; (3) resistance to inhibitors; (4) thermal stability; and (5) low production cost. In addition, a minimized bacterial protein offers the potential benefit of reduced antigenicity. If successful, a minimized and optimized streptokinase will provide a new alternative biopharmaceutical for the thrombolytic therapy market, which is estimated to be worth over $200 million per year in sales. Successful modification of streptokinase will also provide a model for engineering other therapeutic proteins.