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Updated: Sep 25, 2025
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Stretching Short Sequences of DNA with Constant Force Axial Optical Tweezers
Published on: October 13, 2011
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Left versus right: Exploring the effects of chiral threading intercalators using optical tweezers
Adam A Jabak1, Nicholas Bryden1, Fredrik Westerlund2
1Department of Physics, Photonics and Optical Engineering, Bridgewater State University, Bridgewater, Massachusetts.
Biophysical Journal
|April 26, 2022
Summary
Chirality significantly impacts how ruthenium-based DNA-binding drugs interact with cancer cells. The left-handed ΛΛ-P molecule requires more DNA lengthening and binds less effectively than its right-handed counterpart, ΔΔ-P.
Area of Science:
- Biochemistry
- Molecular Biology
- Drug Discovery
Background:
- Small-molecule DNA-binding drugs are vital in cancer therapy.
- Ruthenium-based compounds are promising metal-based drug candidates.
- Understanding DNA-binding mechanisms is key for novel drug design.
Purpose of the Study:
- To investigate the effect of chirality on DNA threading intercalation using ruthenium complexes.
- To compare the DNA-binding properties of left-handed (ΛΛ-P) and right-handed (ΔΔ-P) enantiomers.
- To elucidate nanoscale structural changes and binding kinetics during DNA interaction.
Main Methods:
- Single-molecule optical trapping experiments.
- Analysis of DNA lengthening during binding and unbinding.
- Measurement of association and dissociation rates.
Main Results:
- The left-handed ΛΛ-P complex requires greater DNA lengthening for intercalation compared to ΔΔ-P.
- ΛΛ-P extends DNA more than double the length of ΔΔ-P at equilibrium.
- ΛΛ-P unthreads from DNA three times faster and exhibits weaker binding affinity than ΔΔ-P.
Conclusions:
- Chirality influences DNA binding preference, with a potential affinity for enantiomers matching DNA's inherent chirality.
- These findings enhance understanding of chiral effects in DNA-drug interactions.
- The study offers insights for developing improved chiral metal-based cancer therapeutics.
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