A fusion protein with improved thrombolytic effect and low bleeding risk

Area of Science:

• Biochemistry
• Biotechnology
• Pharmacology

Background:

• Thrombolytic therapy faces a dilemma between treatment efficacy and bleeding risk.
• Combined thrombolytic and anticoagulant treatments increase bleeding complications.
• Need for targeted therapies that balance efficacy and safety.

Purpose of the Study:

• To develop a fusion protein (STH) combining staphylokinase and hirudin.
• To investigate STH's ability to achieve targeted thrombolysis and anticoagulation.
• To assess if STH can reduce bleeding risk compared to combined therapies.

Main Methods:

• Fusion protein STH created by linking staphylokinase to hirudin via a thrombin-cleavable peptide.
• SDS-PAGE and Western blot to confirm thrombin cleavage.
• Amidolytic, thromboelastogram, thrombin-binding, and fibrin clot lysis assays to evaluate activity.
• In vivo animal studies to assess thrombolytic effects and bleeding risk.

Main Results:

• Thrombin specifically cleaved the linker peptide in STH.
• STH exhibited dose-dependent anticoagulant activity upon cleavage, retaining high thrombin affinity.
• STH demonstrated improved thrombolytic efficacy and significantly reduced bleeding risk in animal models.

Conclusions:

• The fusion protein STH effectively targets thrombi, releasing anticoagulant activity locally.
• STH offers a potential therapeutic strategy to improve the efficacy-safety profile of thrombolytic treatments.
• This bifunctional approach may reduce bleeding complications in treating thromboembolic diseases.