Table 2. ITC-Derived Thermodynamic Parameters for Intra-Strand 22-mer and Inter-Strand 12-mer G-Quadruplex–Ligand Interaction at 25 °Ca.
| ligands | n (drug/target) | binding constant Ka × 106 (M–1) | ΔH° (kcal/mol) | TΔS° (kcal/(mol K)) | ΔG° (kcal/mol) |
|---|---|---|---|---|---|
| h-telo22-mer | |||||
| ALI-C3 | 1.06 ± 0.06 | 6.35 ± 0.26 | –8.73 ± 0.03 | –1.07 ± 0.18 | –7.66 ± 0.09 |
| BBZ-ARO | 1.27 ± 0.05 | 8.47 ± 0.65 | –2.26 ± 0.08 | 5.54 ± 0.23 | –7.81 ± 0.41 |
| BBZ-AROCH2 | 1.31 ± 0.04 | 3.41 ± 0.22 | –1.28 ± 0.04 | 6.26 ± 0.08 | –7.54 ± 0.15 |
| BMSG-SH-3 | 1.05 ± 0.03 | 2.92 ± 0.19 | –5.16 ± 1.03 | –8.73 ± 0.17 | –7.47 ± 0.23 |
| h-telo 12-mer | |||||
| ALI-C3 | 0.98 ± 0.11 | 0.61 ± 1.82 | –6.64 ± 0.24 | 0.76 ± 0.13 | –7.41 ± 0.15 |
| BBZ-ARO | 1.03 ± 0.19 | 6.63 ± 2.39 | –1.62 ± 0.43 | 5.97 ± 0.24 | –7.59 ± 0.22 |
| BBZ-AROCH2 | 1.30 ± 0.07 | 0.89 ± 0.11 | –5.13 ± 0.03 | 2.17 ± 0.03 | –7.30 ± 0.17 |
| BMSG-SH-3 | 1.47 ± 0.04 | 2.52 ± 1.47 | –3.57 ± 0.09 | 3.52 ± 0.26 | –7.09 ± 0.04 |
| 2.36 ± 0.05 | 6.96 ± 1.18 | –5.36 ± 0.02 | 1.03 ± 0.07 | –6.39 ± 0.24 | |
| duplex DNA 26-mer | |||||
| ALI-C3 | 1.80 ± 0.20 | 0.03 ± 0.10 | –0.71 ± 0.02 | 6.00 ± 0.12 | –6.70 ± 0.03 |
| BBZ-ARO | 8.00 ± 0.05 | 0.05 ± 0.65 | –2.26 ± 0.08 | 5.59 ± 0.01 | –7.86 ± 1.06 |
| BBZ-AROCH2 | 2.49 ± 0.06 | 0.88 ± 0.63 | –2.04 ± 0.02 | 5.05 ± 0.45 | –7.09 ± 0.25 |
| BMSG-SH-3 | 4.69 ± 0.05 | 0.04 ± 0.01 | –6.67 ± 0.39 | 0.12 ± 0.18 | –6.79 ± 0.37 |
a
The reported Ka and ΔHo values are mean ± SD from three experiments. The values of ΔG° are determined by ΔG° =ΔH° – TΔS°. All ITC profiles were fit to a model of a single binding site except BMSG-SH-3 with h-telo 12-mer quadruplex.