Prothrombin recognition and conformational modulation by anti-thrombin anticoagulant aptamers

Area of Science:

• Biochemistry
• Molecular Biology
• Pharmacology

Background:

• Blood coagulation disorders present significant clinical challenges.
• Development of novel anticoagulant therapeutics is crucial.
• Oligonucleotide aptamers targeting coagulation factors are emerging as potential treatments.

Purpose of the Study:

• To investigate the dual-targeting potential of anti-thrombin aptamers.
• To elucidate the binding mechanisms of aptamers to thrombin and prothrombin.
• To provide insights for the development of new anticoagulant therapies.

Main Methods:

• Calorimetric and spectroscopic analyses were employed.
• Small-angle X-ray scattering (SAXS) studies were integrated.
• Limited proteolysis was utilized to assess structural changes.

Main Results:

• Aptamers were found to recognize proexosite I of prothrombin and exosite I of thrombin.
• Similar thermodynamic binding mechanisms were observed for both targets.
• Aptamer binding to prothrombin induces a conformational shift from closed to open form.

Conclusions:

• The studied aptamers function as dual-targeting agents against thrombin and prothrombin.
• These findings support their potential as effective anticoagulant therapeutics.
• The results offer guidance for further development of aptamer-based anticoagulants.