PLASMINOGEN UROKINASE TYPE MODIFIED ACTIVATOR, DNA SEQUENCE, RECOMBINANT PLASMID, STRAIN-PRODUCER, METHOD FOR PREPARING PLASMINOGEN UROKINASE TYPE MODIFIED ACTIVATOR AND PHARMACEUTICAL COMPOSITION ELICITING THROMBOLYTIC EFFECT

摘要

FIELD: genetic and protein engineering, medicine, molecular biology, pharmacy. ^ SUBSTANCE: invention proposes a modified form of plasminogen urokinase type activator (activator) wherein amino acid sequence differs from that in the natural activator as result of replacing the sequence Arg-Arg-His-Arg-Gly-Gly-Ser in the composition of inhibitory loop for the sequence Arg-His-His-Ala-Gly-Gly-Ser and by replacing 24 N-terminal amino acids for the foreign sequence consisting of 16 amino acid residues. Invention proposes the constructed recombinant plasmid (pUABC 34) comprising DNA fragment that encodes a new activator. As result of transformation of E. coli K-12 JM109 cells with plasmid pUABC 34 the recombinant strain E. coli VKPM-8145 as a producer of a modified form of activator is obtained. This polypeptide is characterized by reduced sensitivity to effect of inhibitor PAI-1 and absence of some by-side effects in the complete retention of biological activity of the natural activator produced by the recombinant. This provides effective applying a new activator as a component of pharmaceutical compositions eliciting thrombolytic effect. ^ EFFECT: valuable medicinal properties of activator and pharmaceutical composition. ^ 6 cl, 6 dwg, 8 ex