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.
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Authors | Y Nakayama, M Shinohara, T Tani, T Kawaguchi, T Furuta, T Izawa, H Kaise, W Miyazaki, Y Nakano |
Journal | Thrombosis and haemostasis
(Thromb Haemost)
Vol. 56
Issue 3
Pg. 364-70
(Dec 15 1986)
ISSN: 0340-6245 [Print] Germany |
PMID | 2951892
(Publication Type: Journal Article)
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Chemical References |
- Fibrinolytic Agents
- Maleimides
- plasmin heavy chain-urokinase conjugate
- maleimide
- Fibrin
- Fibrinolysin
- Urokinase-Type Plasminogen Activator
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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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