8-Oxoguanine Disrupts G-Quadruplex DNA Stability and Modulates FANCJ AKKQ Peptide Binding
Abstract
1. Introduction
2. Results
2.1. G-Quadruplex Conformation and Thermal Stability
2.2. FANCJ AKKQ Binding to 8oxoG4s
3. Discussion
3.1. G4 Conformation and Stability
3.2. FANCJ AKKQ Binding to 8oxoG4s
3.3. Biological Implications and Future Directions
4. Materials and Methods
4.1. Buffers and Reagents
4.2. Peptide and DNA Oligos
4.3. CD Spectroscopy
4.4. Fluorescence Spectroscopy
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
G4 | G-quadruplex |
8oxoG | 8-oxoguanine |
CD | Circular dichroism |
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Name | Conformation | Tm (°C) | ΔTm (°C) |
---|---|---|---|
(GGGT)4 | Parallel | >88.4 ± 8.4 | - |
(GGGT)4 8oxo1 | Parallel | 69.4 ± 0.6 | −19.0 ± 8.4 |
(GGGT)4 8oxo3 | Parallel | 80.3 ± 0.4 | −8.1 ± 8.4 |
(GGGT)4 8oxo5 | Parallel | 71.6 ± 0.4 | −16.8 ± 8.4 |
(GGGTT)4 | Parallel | 83.5 ± 0.7 | - |
(GGGTT)4 8oxo1 | Parallel | 52.0 ± 1.4 | −31.5 ± 1.6 |
(GGGTT)4 8oxo3 | Antiparallel | 57.2 ± 0.3 | −26.3 ± 0.7 |
(GGGTT)4 8oxo5 | Parallel | 55.9 ± 0.3 | −27.6 ± 0.8 |
(TTAGGG)4 | Hybrid | 62.5 ± 0.5 | - |
(TTAGGG)4 8oxo1 | Hybrid-esque | 54.5 ± 0.5 | −8.0 ± 0.7 |
(TTAGGG)4 8oxo3 | Antiparallel | 49.5 ± 0.3 | −13.0 ± 0.6 |
(TTAGGG)4 8oxo5 | Hybrid-esque | 38.9 ± 0.6 | −23.6 ± 0.8 |
Name | Conformation | Tm (°C) | ΔTm (°C) |
---|---|---|---|
(GGGT)4 | Parallel | 70.3 ± 0.7 | - |
(GGGT)4 8oxo1 | Parallel | 42.5 ± 0.5 | −27.8 ± 0.9 |
(GGGT)4 8oxo3 | Parallel | 56.4 ± 0.4 | −13.9 ± 0.8 |
(GGGT)4 8oxo5 | Parallel | 44.0 ± 0.3 | −26.3 ± 0.8 |
(GGGTT)4 | Parallel | 44.8 ± 1.2 | - |
(GGGTT)4 8oxo1 | Antiparallel | 47.2 ± 0.3 | 2.4 ± 1.2 |
(GGGTT)4 8oxo3 | Antiparallel | 44.6 ± 0.2 | −0.2 ± 1.2 |
(GGGTT)4 8oxo5 | Hybrid-esque | 27.5 ± 0.9 | −17.3 ± 1.4 |
(TTAGGG)4 | Antiparallel | 52.1 ± 0.3 | - |
(TTAGGG)4 8oxo1 | Antiparallel | 47.8 ± 0.6 | −4.3 ± 0.7 |
(TTAGGG)4 8oxo3 | Antiparallel | 42.2 ± 0.7 | −9.9 ± 0.8 |
(TTAGGG)4 8oxo5 | Antiparallel | 33.3 ± 0.4 | −18.8 ± 0.5 |
Name | K (M−1) | R2 |
---|---|---|
GGGT)4 | 2.7 ± 0.4 × 105 | 0.997 |
(GGGT)4 8oxo1 | 7.7 ± 0.7 × 105 | 0.998 |
(GGGT)4 8oxo3 | 3.2 ± 0.1 × 105 | 0.997 |
(GGGT)4 8oxo5 | 4.4 ± 0.6 × 105 | 0.997 |
(GGGTT)4 | 6.0 ± 0.9 × 105 | 0.997 |
(GGGTT)4 8oxo1 | 8.2 ± 1.0 × 105 | 0.997 |
(GGGTT)4 8oxo3 | 9.6 ± 1.0 × 105 | 0.996 |
(GGGTT)4 8oxo5 | 9.3 ± 0.8 × 105 | 0.997 |
(TTAGGG)4 | 1.6 ± 0.7 × 106 | 0.996 |
(TTAGGG)4 8oxo1 | 1.3 ± 0.4 × 106 | 0.997 |
(TTAGGG)4 8oxo3 | 1.2 ± 0.1 × 106 | 0.996 |
(TTAGGG)4 8oxo5 | 1.4 ± 0.5 × 106 | 0.997 |
Name | K (M−1) | R2 |
---|---|---|
(GGGT)4 | 2.3 ± 0.3 × 105 | 0.9997 |
(GGGT)4 8oxo1 | 3.4 ± 0.5 × 105 | 0.9996 |
(GGGT)4 8oxo3 | 2.9 ± 0.5 × 105 | 0.9994 |
(GGGT)4 8oxo5 | 3.4 ± 0.5 × 105 | 0.9997 |
(GGGTT)4 | 4.9 ± 2.0 × 105 | 0.9995 |
(GGGTT)4 8oxo1 | 3.9 ± 1.3 × 105 | 0.9993 |
(GGGTT)4 8oxo3 | 5.2 ± 1.7 × 105 | 0.9994 |
(GGGTT)4 8oxo5 | 5.6 ± 1.1 × 105 | 0.9992 |
(TTAGGG)4 | 6.5 ± 0.6 × 105 | 0.9991 |
(TTAGGG)4 8oxo1 | 6.5 ± 1.4 × 105 | 0.9996 |
(TTAGGG)4 8oxo3 | 5.1 ± 1.1 × 105 | 0.9998 |
(TTAGGG)4 8oxo5 | 1.1 ± 0.1 × 106 | 0.9974 |
Name | Sequence (5′→3′) | Molar Extinction Coefficient (M−1·cm−1) | Molecular Weight (g/mol) |
---|---|---|---|
(GGGT)4 | GGGTGGGTGGGTGGGT | 157,200 | 5105.3 |
(GGGT)4 8oxo1 | T/i8oxodG/GGTGGGTGGGTGGGT | 159,100 | 5425.5 |
(GGGT)4 8oxo3 | GG/i8oxodG/TGGGTGGGTGGGT | 151,600 | 5121.3 |
(GGGT)4 8oxo5 | GGGTG/i8oxodG/GTGGGTGGGT | 151,600 | 5121.3 |
(GGGTT)4 | GGGTTGGGTTGGGTTGGGTT | 189,600 | 6322.1 |
(GGGTT)4 8oxo1 | /i8oxodG/GGTTGGGTTGGGTTGGGTT | 184,000 | 6338.1 |
(GGGTT)4 8oxo3 | GG/i8oxodG/TTGGGTGGGTTGGGTT | 184,000 | 6338.1 |
(GGGTT)4 8oxo5 | GGGTTG/i8oxodG/GTTGGGTTGGGTT | 184,000 | 6338.1 |
(TTAGGG)4 | TTAGGGTTAGGGTTAGGGTTAGGG | 244,600 | 7575.0 |
(TTAGGG)4 8oxo1 | TTA/i8oxodG/GGTTAGGGTTAGGGTTAGGG | 239,000 | 7590.9 |
(TTAGGG)4 8oxo3 | TTAGG/i8oxodG/TTAGGGTTAGGGTTAGGG | 239,000 | 7590.9 |
(TTAGGG)4 8oxo5 | TTAGGGTTAG/i8oxodG/GTTAGGGTTAGGG | 239,000 | 7590.9 |
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Campbell, L.; Lowran, K.; Cismas, E.; Wu, C.G. 8-Oxoguanine Disrupts G-Quadruplex DNA Stability and Modulates FANCJ AKKQ Peptide Binding. Molecules 2025, 30, 3424. https://doi.org/10.3390/molecules30163424
Campbell L, Lowran K, Cismas E, Wu CG. 8-Oxoguanine Disrupts G-Quadruplex DNA Stability and Modulates FANCJ AKKQ Peptide Binding. Molecules. 2025; 30(16):3424. https://doi.org/10.3390/molecules30163424
Chicago/Turabian StyleCampbell, Laura, Kaitlin Lowran, Emma Cismas, and Colin G. Wu. 2025. "8-Oxoguanine Disrupts G-Quadruplex DNA Stability and Modulates FANCJ AKKQ Peptide Binding" Molecules 30, no. 16: 3424. https://doi.org/10.3390/molecules30163424
APA StyleCampbell, L., Lowran, K., Cismas, E., & Wu, C. G. (2025). 8-Oxoguanine Disrupts G-Quadruplex DNA Stability and Modulates FANCJ AKKQ Peptide Binding. Molecules, 30(16), 3424. https://doi.org/10.3390/molecules30163424