Related Experiment Video
Updated: Oct 7, 2025
08:09
Mapping the Binding Site of an Aptamer on ATP Using MicroScale Thermophoresis
Published on: January 7, 2017
10.8K
Improving Structural Stability and Anticoagulant Activity of a Thrombin Binding Aptamer by Aromatic Modifications
Nathalie Busschaert1,2, Debabrata Maity1, Pralok K Samanta3,4
1Department of Chemistry, New York University, New York, New York, 10003, USA.
Chembiochem : a European Journal of Chemical Biology
|January 5, 2022
Summary
Terminal modification of DNA aptamers with aromatic dyes like PDI enhances their G-quadruplex stability and anticoagulant properties. This structural improvement leads to significantly increased melting temperatures and improved therapeutic potential for thrombin binding aptamers.
Area of Science:
- Biochemistry
- Molecular Biology
- Medicinal Chemistry
Background:
- The thrombin binding aptamer (TBA) is a DNA oligonucleotide that forms a G-quadruplex structure.
- TBA exhibits anticoagulant properties by binding to thrombin's fibrinogen-recognition exosite.
Purpose of the Study:
- To investigate the effect of terminal modification of TBA with aromatic fragments on G-quadruplex stability.
- To evaluate the impact of these modifications on the aptamer's anticoagulant activity.
Main Methods:
- Terminal functionalization of TBA with coumarin, pyrene, and perylene diimide (PDI).
- Assessment of G-quadruplex stability using melting temperature (Tm) measurements.
- Evaluation of anticoagulant activity of modified aptamers.
Main Results:
- Aromatic modifications, particularly with PDI, significantly improved G-quadruplex stability.
- MonoPDI-functionalized TBA showed the most substantial increase in melting temperature (ΔTm ≈ +18°C).
- Enhanced stability correlated with improved anticoagulant activity.
Conclusions:
- Terminal aromatic modification is an effective strategy to stabilize TBA G-quadruplex structures.
- PDI-modified TBA demonstrates superior stability and enhanced anticoagulant efficacy.
- These findings suggest potential for developing more potent anticoagulant aptamer-based therapeutics.
Related Concept Videos
02:36Transfer RNA Synthesis
12.3K
One of the unique features of tRNA is the presence of modified bases. In some tRNAs, modified bases account for nearly 20% of the total bases in the molecule. Altogether, these unusual bases protect the tRNA from enzymatic degradation by RNases.
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
12.3K
01:18Basicity of Aromatic Amines
7.4K
The basicity of aromatic amines is much weaker than that of aliphatic amines due to the involvement of the lone pair of electrons over the N atom in resonance with the aryl rings. Generally, the electron-donating ability of any substituents on the aryl ring of aromatic amines increases the basicity of the amine by increasing electron density, and hence the availability of lone pair on the nitrogen. On the other hand, electron-withdrawing functional groups on the aryl ring of amines decrease the...
7.4K