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The plasmin heavy chain-urokinase conjugate: a specific thrombolytic agent.

Abstract
Low molecular weight urokinase (LMW-UK) was coupled to the heavy chain of plasmin to make it able to bind to fibrin. The purified conjugate (PHC-UK conjugate), which consisted of equimolar concentrations of each starting material had a molecular weight of 93,600, bound tightly to fibrin-monomer-Sepharose and was not washed off with 1 M NaCl, but was eluted specifically with epsilon-amino caproic acid. The conjugate showed higher fibrinolytic activity than HMW-UK. A control conjugate prepared by coupling human serum albumin to LMW-UK (HSA-UK conjugate) showed the same fibrinolytic activity as HMW-UK. The half-lives of these two conjugates in rabbits were about 3 times that of HMW-UK. In an experimental pulmonary embolism model in rabbits, the PHC-UK conjugate showed about 10 times higher thrombolytic activity than HMW-UK, while the HSA-UK conjugate showed similar thrombolytic activity as HMW-UK, and moreover caused severe systemic fibrinogen breakdown. Thus the significant increase in thrombolytic activity after injection of PHC-UK conjugate into rabbits may be due to its newly acquired fibrin binding activity, and not to increase in its half-life. It is concluded that the PHC-UK conjugate may be useful in treatment of thrombosis.
AuthorsY Nakayama, M Shinohara, T Tani, T Kawaguchi, T Furuta, T Izawa, H Kaise, W Miyazaki, Y Nakano
JournalThrombosis and haemostasis (Thromb Haemost) Vol. 56 Issue 3 Pg. 364-70 (Dec 15 1986) ISSN: 0340-6245 [Print] Germany
PMID2951892 (Publication Type: Journal Article)
Chemical References
  • Fibrinolytic Agents
  • Maleimides
  • plasmin heavy chain-urokinase conjugate
  • maleimide
  • Fibrin
  • Fibrinolysin
  • Urokinase-Type Plasminogen Activator
Topics
  • Animals
  • Body Burden
  • Fibrin (metabolism)
  • Fibrinolysin (isolation & purification, metabolism, pharmacology, therapeutic use)
  • Fibrinolytic Agents (pharmacology)
  • Maleimides (pharmacology)
  • Protein Binding
  • Protein Conformation
  • Rabbits
  • Thrombosis (drug therapy)
  • Urokinase-Type Plasminogen Activator (isolation & purification, metabolism, pharmacology, therapeutic use)

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