A recombinant prodrug type approach for triggered delivery of streptokinase.
A novel prodrug type approach for triggered delivery of thrombolytic drugs without their associated hemorrhagic effects has been proposed. Presented herein is a rapid communication of preliminary observations that suggest the feasibility of the approach. A hirulog-streptokinase fusion protein (termed "HSK") possessing active thrombolytic functions has been successfully produced using recombinant DNA technology. The prodrug and triggered release features of this approach have been demonstrated by the inhibition of the plasminogen-activating activity of HSK via binding with thrombin and reversal of this inhibition by hirudin.
Wang
H
H
College of Pharmacy, The University of Michigan, Ann Arbor, MI 48109-1065, USA.
Song
H
H
Yang
V C
VC
D000595:Amino Acid Sequence; D000991:Antithrombins / Q000138:chemical synthesis* / Q000494:pharmacology; D001665:Binding Sites; D005343:Fibrinolytic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D006629:Hirudins / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D010958:Plasminogen / Q000378:metabolism; D011355:Prodrugs / Q000138:chemical synthesis* / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D013300:Streptokinase / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology
D000991:Antithrombins; D005343:Fibrinolytic Agents; D006629:Hirudins; D010446:Peptide Fragments; D011355:Prodrugs; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D010958:Plasminogen; D013300:Streptokinase; C074619:bivalirudin