Table 2.
IC50 of macrocyclic peptides against Mtb20SOG and β5c and β5i of the human c-20S and i-20Sa
 | ||||||||
|---|---|---|---|---|---|---|---|---|
| Proteasome inhibition | ||||||||
| Macrocycle | Linker type | R1 | R2 | IC50 (μM) | SIapp* | |||
| Mtb20S | β5c | β5i | IC50–β5c | IC50–β5i | ||||
| IC50-Mtb20S | IC50-Mtb20S | |||||||
| CP1 | - | - | - | >100 | >100 | >100 | - | - |
| 5 | 1 |  |
H | 0.20 ± 0.05 | >100 | 21.1 ± 5.2 | >500 | 108 |
| 6 | 1 |  |
H | 0.0074 ± 0.0012 | >100 | >100 | >13,600 | >13,600 |
| 7 | 1 |  |
 |
0.17 ± 0.02 | >100 | >100 | >594 | >594 |
| 8 | 1 |  |
 |
0.84 ± 0.08 | >100 | >100 | >119 | >119 |
| 9 | 2 |  |
H | 0.007 ± 0.001 | >100 | >100 | >14,000 | >14,000 |
| 10 | 3 |  |
H | 0.007 ± 0.003 | >100 | >100 | >14,400 | >14,400 |
| 11 | 3 |  |
H | 0.007 ± 0.0004 | 0.073 ± 0.002 | 0.069 ± 0.028 | 11 | 11 |
| 12 | 3 |  |
H | 0.079 ± 0.014 | 1.5 ± 0.1 | 0.87 ± 0.37 | 19 | 11 |
| 13 | 3 |  |
H | 1.5 ± 0.2 | 86.2± 12.1 | 47.3 ± 4.9 | 57 | 31 |
a
Data are the mean of at least three independent experiments. LLVY: suc-LLVY-AMC, used for all three proteasomes. SIapp: apparent selectivity index.
*
SI values were rounded to 3 or fewer significant figures.