Mechanism of DNA Intercalation by Chloroquine Provides Insights into Toxicity
Abstract
:1. Introduction
2. Results
2.1. Force Extension of dsDNA + Chloroquine in Optical Tweezers
2.2. Characterizing Chloroquine Binding to dsDNA
2.3. Chloroquine Binding to ssDNA Is Weaker Than to B-DNA
2.4. Chloroquine Intercalation Stabilizies B-DNA
2.5. AFM Measures Distinct Binding Modes
2.6. Chloroquine Increases dsDNA Melting Temperature
2.7. Chloroquine-B DNA Binding Is Entropically Driven and Endothermic
3. Discussion
4. Materials and Methods
4.1. Samples and Solutions
4.2. Optical Tweezers
4.3. Models of Polymer Elasticity
4.4. Deducing Binding Affinity
4.5. Calculating the Energy of Overstretching
4.6. Atomic Force Microscopy
4.7. Thermal Melting Studies
4.8. Isothermal Titration Calorimetry
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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Na+ Concentration (mM) | KD (µM) | Experimental Method |
---|---|---|
20 | 90 ± 10 | thermal melting |
30 | 360 ± 20 | isothermal titration calorimetry |
100 | 650 ± 150 | thermal melting |
100 | 170 ± 90 | optical tweezers |
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Joshi, J.; McCauley, M.J.; Morse, M.; Muccio, M.R.; Kanlong, J.G.; Rocha, M.S.; Rouzina, I.; Musier-Forsyth, K.; Williams, M.C. Mechanism of DNA Intercalation by Chloroquine Provides Insights into Toxicity. Int. J. Mol. Sci. 2024, 25, 1410. https://doi.org/10.3390/ijms25031410
Joshi J, McCauley MJ, Morse M, Muccio MR, Kanlong JG, Rocha MS, Rouzina I, Musier-Forsyth K, Williams MC. Mechanism of DNA Intercalation by Chloroquine Provides Insights into Toxicity. International Journal of Molecular Sciences. 2024; 25(3):1410. https://doi.org/10.3390/ijms25031410
Chicago/Turabian StyleJoshi, Joha, Micah J. McCauley, Michael Morse, Michael R. Muccio, Joseph G. Kanlong, Márcio S. Rocha, Ioulia Rouzina, Karin Musier-Forsyth, and Mark C. Williams. 2024. "Mechanism of DNA Intercalation by Chloroquine Provides Insights into Toxicity" International Journal of Molecular Sciences 25, no. 3: 1410. https://doi.org/10.3390/ijms25031410