Biologically active mutant tissue plasminogen activators are disclosed wherein site directed mutagenesis, for example, of a two-chain activation site, especially in the region of residues 270-279, renders said mutants resistant to conversion to the two-chain form.
Particularly preferred mutations are substitution of arge- nine at residue 275 and/or isoleucine at residue 276.
本研究公开了具有
生物活性的突变型组织纤溶酶原激活剂,通过对双链激活位点,特别是残基 270-279 区域的位点定向诱变,使所述突变体具有向双链形式转化的抗性。
特别优选的突变是取代残基 275 中的 arge- nine 和/或残基 276 中的
异亮氨酸。