Related Experiment Videos
Favorable 2'-substitution in the loop region of a thrombin-binding DNA aptamer
Ragini Awachat1, Atish A Wagh1, Manisha Aher1
1Organic Chemistry Division, CSIR-National Chemical Laboratory, Homi Bhabha Road, Pashan, Pune 411008, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-NCL Campus, Pune 411008, India.
Bioorganic & Medicinal Chemistry Letters
|April 22, 2018
Summary
Simple chemical modifications stabilize a G-quadruplex structure in a thrombin-binding aptamer. This enhanced stability significantly increases the inhibition of thrombin-induced fibrin polymerization, impacting blood-clotting processes.
Area of Science:
- Biochemistry
- Molecular Biology
- Medicinal Chemistry
Background:
- Thrombin-binding aptamers (TBAs) are crucial in regulating blood-clotting.
- G-quadruplex structures are key to TBA functionality.
- Chemical modifications can enhance aptamer stability and efficacy.
Purpose of the Study:
- To investigate the impact of 2'-OMe chemical modifications on the G-quadruplex structure of a 15mer G-rich DNA sequence.
- To determine if these modifications enhance the stability of the thrombin-binding aptamer (TBA).
- To evaluate the effect of structural stabilization on the inhibition of thrombin-induced fibrin polymerization.
Main Methods:
- Synthesis of a 15mer G-rich DNA sequence with a specific 2'-OMe modification in the loop region.
- Structural analysis of the modified G-quadruplex.
- Assay of thrombin-induced fibrin polymerization inhibition.
Main Results:
- A single 2'-OMe modification (T → 2'-OMe-U) at specific positions stabilized the G-quadruplex structure of the TBA.
- The position of the modification influenced the degree of structural stabilization.
- Stabilized TBA demonstrated significantly increased inhibition of thrombin-induced fibrin polymerization.
Conclusions:
- 2'-OMe chemical modifications are effective in stabilizing G-quadruplex structures in TBAs.
- Enhanced structural stability correlates with improved inhibition of blood-clotting.
- This strategy holds potential for developing novel anticoagulant therapeutics.