Effect of Locked-Nucleic Acid on a Biologically Active G-Quadruplex. A Structure-Activity Relationship of the Thrombin Aptamer
2008

Effect of Locked-Nucleic Acid on Thrombin Aptamer Activity

publication Evidence: moderate

Author Information

Author(s): Bonifacio Laura, Church Frank C., Jarstfer Michael B.

Primary Institution: University of North Carolina at Chapel Hill

Hypothesis

Can locked nucleic acid (LNA) substitutions enhance the biological activity of the thrombin aptamer?

Conclusion

LNA substitutions at certain positions in the thrombin aptamer can decrease its thrombin inhibition activity despite increasing thermal stability.

Supporting Evidence

  • LNA substitutions at positions G5, T7, or G8 reduced thrombin inhibition.
  • LNA at position G2 showed activity comparable to the un-substituted aptamer.
  • The thermal stability of substituted aptamers did not correlate with their activity.

Takeaway

This study looked at how changing parts of a special DNA can affect its ability to stop blood clots. Some changes made it work worse, even if it was more stable.

Methodology

The study used fibrinogen clotting assays and heparin template curve assays to evaluate the biological activity of LNA-substituted thrombin aptamers.

Limitations

The study did not measure the melting temperature for the aptamer with LNA in position T4 due to its instability.

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