G-quadruplex-based aptamers targeting human thrombin: Discovery, chemical modifications and antithrombotic effects

Area of Science:

• Biochemistry
• Molecular Biology
• Pharmacology

Background:

• Thrombin-binding aptamers (TBAs), like the G-quadruplex-forming HD1, inhibit thrombin by targeting exosite I.
• Unmodified aptamers have poor in vivo stability due to nuclease degradation, limiting their therapeutic use.

Purpose of the Study:

• To review the current state of DNA aptamers targeting thrombin.
• To focus on chemically modified aptamer analogues and their therapeutic potential.

Main Methods:

• Literature review of thrombin-inhibiting DNA aptamers.
• Focus on chemical modifications of aptamer backbones (nucleobases, sugars, linkages).
• Analysis of optimized aptamer analogues and their biological performance.

Main Results:

• Numerous anticoagulant aptamers have been discovered since 1992.
• Chemical modifications significantly enhance aptamer pharmacokinetic properties and stability.
• Optimized aptamers, including G4 structures and bivalent constructs, show therapeutic promise.

Conclusions:

• Chemically modified DNA aptamers offer improved biological performance for anticoagulant applications.
• Thrombin-binding aptamers represent a promising area for developing novel therapeutic agents.
• Continued research in this field is crucial for advancing anticoagulant therapies.