Table 1.
Binding Affinities of Ac-ARA-NH2 Analogues Designed to Investigate the P1, P2, and P4 Sites in WDR5a
| A1 modifications
|
R2 modifications
|
A3 modifications
|
||||||
|---|---|---|---|---|---|---|---|---|
| peptide | IC50 ± SD (μM) | Ki ± SD (μM) | peptide | IC50 ± SD (μM) | Ki ± SD (μM) | peptide | IC50 ± SD (μM) | Ki ± SD (μM) |
| 1a, GRA | 77.4 ± 13.2 | 16.7 ± 2.8 | 2a, AN1eA | >300 | >65 | 3a, ARG | 10.3 ± 1.2 | 2.2 ± 0.3 |
| 1b, AbuRA | 0.28 ± 0.02 | 0.06 ± 0.001 | 2b, AOrnA | >300 | >65 | 3b, ARAbu | 0.03 ± 0.008 | 0.006 ± 0.002 |
| 1c, VRA | 0.24 ± 0.03 | 0.05 ± 0.005 | 2c, AKA | >300 | >65 | 3c, ARV | 0.11 ± 0.02 | 0.02 ± 0.003 |
| 1d, CRA | 1.83 ± 0.30 | 0.4 ± 0.6 | 2d, ACitA | >300 | >65 | 3d, ARC | 0.08 ± 0.01 | 0.02 ± 0.003 |
| 1e, LRA | 10.8 ± 0.40 | 2.3 ± 0.3 | 3e, ARL | 34 ± 6 | 7.3 ± 1.2 | |||
| 1f, ChgRA | 8.7 ± 0.60 | 1.9 ± 0.1 | 3f, ARChg | 280 ± 70 | 61 ± 16 | |||
| 1g, HRA | 1.7 ± 0.3 | 0.4 ± 0.03 | 3g, ARF | 280 ± 40 | 60 ± 8 | |||
| 1h, FRA | 3.1 ± 0.3 | 0.7 ± 0.07 | 3h, ARS | 1.8 ± 0.03 | 0.4 ± 0.07 | |||
| 1i, SRA | 2.9 ± 0.61 | 0.6 ± 0.1 | 3i, ART | 0.08 ± 0.003 | 0.02 ± 0.001 | |||
| 1j, TRA | 2.9 ± 0.4 | 0.6 ± 0.09 | 3j, ARE | >100 | >20 | |||
a
For ARA, IC50 = 0.54 ± 0.03 μM, Ki = 0.12 ± 0.01 μM. Abbreviations: 2-Abu, 2-aminobutyric acid; Chg, cyclohexylglycine; Nle, nor-leucine; Orn, ornithine; Cit, citrulline.