| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T135 |
0-449 |
Sentence |
denotes |
Peptidyl HMK inhibitors and their corresponding ethers have been designed as potent reversible cysteine protease inhibitors of cathepsin K34 and cruzain.43 High-resolution crystal structures of two such inhibitors complexed with cruzain highlighted the presence of a strong hydrogen bond between the catalytic His and the α-hydroxyl moiety of the inhibitor but interestingly no covalent bond between the active-site Cys and the ketone pharmacophore. |
| T136 |
450-793 |
Sentence |
denotes |
Utilizing the crystal structure of 28 in complex with SARS CoV-1 3CLpro, molecular modeling of an HMK-based design indicated the potential for establishing a covalent bond between the sulfur of the active-site cysteine (Cys145) and the HMK carbonyl as well as hydrogen bond interactions between catalytic His41 and the terminal hydroxy moiety. |
| T137 |
794-966 |
Sentence |
denotes |
Additionally, the structure of 28 suggested the possibility to increase the lipophilic filling of the deep hydrophobic S2 pocket as a strategy to increase binding affinity. |
| T138 |
967-1114 |
Sentence |
denotes |
To evaluate these structure-based observations, a series of reversible HMK inhibitors containing P2 diversity were prepared as depicted in Table 3. |
