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Leeches to hirulogs and other thrombin-directed antithrombotics
1New York State Department of Health, Wadsworth Center for Laboratories and Research, Albany.
Hematology/Oncology Clinics of North America
|October 1, 1992
Summary
Medicinal leeches are resurging in surgery, offering hirudin, a potent antithrombotic. This protein inspired new thrombin inhibitors, though small molecules may eventually replace them.
Area of Science:
- Biochemistry
- Pharmacology
- Medical Science
Background:
- Leeches have a long history of medicinal use, including bloodletting.
- Modern medicine saw a decline in leeching, but it has resurged in reconstructive surgery.
- The European medicinal leech produces hirudin, a key antithrombotic protein.
Purpose of the Study:
- To explore the development of antithrombotic therapies derived from leech compounds.
- To investigate the mechanism of hirudin's interaction with thrombin.
- To discuss the potential and limitations of hirudin-based anticoagulants.
Main Methods:
- Cloning of the hirudin protein.
- Development of the bridge-binding double-ligand concept.
- Investigation of hirulog class thrombin inhibitors.
- Exploration of alternative antithrombotic strategies targeting thrombin.
Main Results:
- Hirudin was identified as a potent antithrombotic substance.
- The study of hirudin-thrombin interactions led to the development of hirulogs.
- Hirulogs and recombinant hirudins show promise but are not orally active.
- Thrombin's central role in thrombosis and hemostasis makes it a key therapeutic target.
Conclusions:
- Hirudin and hirulog-class inhibitors represent significant advancements in antithrombotic therapy.
- While effective, these therapies face potential replacement by future small-molecule inhibitors.
- Targeting thrombin's cellular functions offers another avenue for antithrombotic intervention.