Minimized Streptokinase

描述（由申请人提供）：我们建议创建一个最小化和 相对于已知的具有改进性质的修饰的链激酶 目前用于溶栓治疗的纤溶酶原激活剂。新方法 由KAIROS开发，用于蛋白质最小化和高通量筛选， 酶变体将被用于发现天然蛋白质的较小版本 对含纤维蛋白的凝块有最大的活性。最小化的 链激酶（mSK）将被设计为具有：（1）增加的特异性， 纤维蛋白;（2）增加对纤溶酶和其它蛋白酶降解的抗性; (3)对抑制剂的抗性;（4）热稳定性;和（5）低产量 成本此外，最小化的细菌蛋白质提供了潜在的好处， 抗原性降低。如果成功，最小化和优化的链激酶 将为溶栓治疗提供一种新的替代生物制剂 市场，估计每年销售额超过2亿美元。 链激酶的成功修饰也将提供一个模型， 改造其他治疗性蛋白质。

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.