Figure 1.
Structure of compounds 1–7.
Figure 2.
Sensorgrams obtained by injecting different concentrations (from 0.020 to 1 µM) of 1 (A), 2 (B), 3 (C), 4 (D), 5 (E), 6 (F) 7 (G) and radiciol (H) on immobilized Hsp90.
Table 1.
Thermodynamic and kinetic constants measured by SPR for the interaction between tested compounds and immobilized HSP90.
Figure 3.
Inhibition of the ATPase activity of Hsp90 by different concentration of compounds 1–4.
Radicicol and 17-AAG were used as positive controls. Data are the mean of two independent experiments performed in triplicate and were analyzed by t test (Hsp90 vs Hsp90+ testing compound): *P<0.05, **P<0.005.
Figure 4.
Aggregation kinetics of CS at 43°C determined by light scattering.
The spontaneous aggregation of CS at 43°C (♦) and the aggregation of CS at 43°C in the presence of 0.075 µM Hsp90 (Δ) or of 0.075 µM Hsp90 and 0.3 µM compound 1 (▪), 0.3 µM compound 2 (•), 0.3 compound 3 (□), or 0.3 µM compound 4 (○) are shown.
Figure 5.
Schematic representation of the results obtained from limited proteolysis experiments.
The preferential cleavage sites detected on recombinant Hsp90, and on the Hsp90/1 complex are in black. The Hsp90 N-terminal domain is highlighted in light grey, the middle domain is boxed and the C-terminal domain is highlighted in grey.
Figure 6.
Three dimensional models (A and B) of (+)-lentiginosine (1, yellow) and (−)-lentiginosine (2, green) with HSP90. The target molecule is depicted by sky blue ribbon and the crucial amino acids by cpk (by atom type: C, purple; O, red; N, dark blue, H, white).