Table 6. Inhibitory Activity of Dipeptide Alkynes with or without a Free Carboxylic Group at P1 with Respect to Cathepsins B, L, S, and Ka.
|
kinact/KI (M–1 s–1) |
|||||||
|---|---|---|---|---|---|---|---|
| compound | R1 | R2 | R3 | CatB | CatS | CatL | CatK |
| 2b | 4-fluorobenzoyl | Me | H | 85(3) | 682(85) | 281(30) | 48(5) |
| 63 | Me | n.i. | 12(2) | 79(13) | n.i. | ||
| 2f | 3-iodobenzoyl | Me | H | 45(1) | n.i. | 1968(153) | n.i. |
| 64 | Me | 15(2) | 137(9) | 537(18) | n.i. | ||
| 2k | 4-fluorobenzoyl | I | H | 1179(222) | 10133(842) | 2128(230) | 121(5) |
| 53k | allyl | 141(19) | 3589(79) | 1246(116) | n.i. | ||
a
The measurement was performed in three independent experiments (each as a duplicate determination) in assay buffer (pH 6.0) with 1.5% DMSO. n.i. = no inhibition; i.e., no evidence of irreversible inhibition was discernible within the considered time and concentration ranges. Data shown are mean values ± SEM of three experiments, each performed in duplicate.