A novel thrombin binding aptamer containing a G-LNA residue

Area of Science:

• Biochemistry
• Molecular Biology
• Medicinal Chemistry

Background:

• Thrombin binding aptamers (TBAs) are crucial in anticoagulation therapy.
• Modifications to TBAs can alter their structural and pharmacological properties.

Purpose of the Study:

• To investigate the structure, thermodynamics, and pharmacological activity of a novel G-LNA modified TBA.
• To characterize the three-dimensional structure and folding patterns of the modified aptamer.

Main Methods:

• Nuclear Magnetic Resonance (NMR) and Circular Dichroism (CD) spectroscopy.
• Molecular dynamics and molecular mechanics calculations.
• Thermodynamic studies and assessment of pharmacological properties.

Main Results:

• The modified TBA, d(5'-GGTTGGTGTGGTTGg-3'), adopts a chair-like structure with two G-tetrads linked by TT, TGT, and TT loops.
• The aptamer displays parallel and antiparallel strand arrangements, resulting in specific syn-anti arrangements of guanine bases.
• The modified TBA retains anticoagulant activity, albeit at a reduced level compared to the unmodified TBA.

Conclusions:

• The G-LNA modification results in a stable, chair-like structure for the TBA.
• The modified TBA possesses functional anticoagulant properties, indicating potential for therapeutic applications.
• Structural and thermodynamic characterization provides insights into aptamer design for improved pharmacological profiles.