Table 2.
Compound | Linker | Estimated length between ligands (Å)a | IC50 (nM) | Relative potency to Ac-MSH(4) |
---|---|---|---|---|
Ac-MSH(4) | - | - | 4600 ± 790 | - |
NB300 | (Gly-Pro)3 | 60±20 | 620 ± 51 | 7 |
NB299 | (Gly-Pro)2 | 52±20 | 410 ± 70 | 11 |
NB298 | (Gly-Pro)1 | 45±20 | 220 ± 59 | 21 |
NB302 | (β-Ala)2 | 48±10 | 120 ± 10 | 38 |
NB301 | β-Ala | 43±10 | 88 ± 12 | 52 |
NB297 | No linker | 35±10 | 71 ± 5.3 | 64 |
NB342 | β-Ala | 35±5 | 73 ± 3.5 | 63 |
NB341 | No linker | 24±5 | 14 ± 1.5 | 330 |
Competition experiments were carried out using time resolved fluorescence31. Multimers were competed against Eu-NDP-α-MSH. The IC50 values are the average of 4 experiments each done in quadruplicate.
Linker length was estimated from an energy-minimized structure using MacroModel.