Table 1. Biophysical characterization of designed p53-Y220C ligands.
| compound | DSF ΔTm [K] at 250 μMa |
NMR KD [μM] | ITC KD [μM] |
|---|---|---|---|
| 2 | n.d. | 819 ± 68 | n.d. |
| 3 | 0.55 | 184 ± 23 | 225 |
| 4 | 0.97 | 104 ± 23 | 105 |
| 5 | 1.10 | 87 ± 17 | 78 |
| 6 | 0.31 | 247 ± 44 | n.d. |
| 7 | 0.03 | 1040 ± 160 | n.d. |
| 8 | –0.05 | 4900 ± 2300 | n.d. |
| 9 (PhiKan5116) | 0.58 | 114 ± 8 | 107 |
| 10 | 0.64 | 1080 ± 360 | n.d. |
| 11 (PhiKan5174) | 3.21 | n.a.b | 15.5 |
| 12 (PhiKan5176) | 2.59 | n.a.b | 20.6 |
| 13 (PhiKan5196) | 3.61 | n.a.b | 9.7 |
a
ΔTm =Tm(ligand-bound protein) – Tm(free protein).
b
For binders with a KD in the low micromolar region, line broadening (intermediate exchange) was observed instead of chemical shift perturbation.