Table 1. Design and Mdm2 Binding Properties of Preliminary Oxopiperazine-Derived Helix Mimetics.
mimetic | R1 | R2 | R3 | R4 | X | Kd (μM)a |
---|---|---|---|---|---|---|
1 | Phe | Trp | Ala | Leu | OH | 65 ± 8 |
2 | Phe | Trp | Lys | Leu | OH | ≥200 |
3 | Phe | Trp | Leu | Leu | OH | 7.9 ± 0.5 |
4 | Phe | Trp | Phe | Leu | OH | 6.9 ± 1.3 |
5 | Phe | Trp | Phe | Leu | NH2 | 2.9 ± 0.1 |
6 | Phe | Trp | Phe | Lys | NH2 | ≥200 |
7 | Lys | Trp | Phe | Leu | NH2 | ≥200 |
8 | Phe | Ala | Phe | Leu | NH2 | 64 ± 7 |
Binding affinity for Mdm2 as determined by a competitive fluorescence polarization assay.