Peptide Ketobenzoxazole Inhibitors Bound to Cathepsin K
- 1 December 2003
- journal article
- research article
- Published by American Chemical Society (ACS) in Biochemistry
- Vol. 42 (51) , 15018-15028
- https://doi.org/10.1021/bi035041x
Abstract
Potent inhibitors of human cysteine proteases of the papain family have been made and assayed versus a number of relevant family members. We describe the synthesis of peptide α-ketoheterocyclic inhibitors that occupy binding subsites S1‘-S3 of the cysteine protease substrate recognition cleft and that form a reversible covalent bond with the Cys 25 nucleophile. X-ray crystal structures of cathepsin K both unbound and complexed with inhibitors provide detailed information on protease/inhibitor interactions and suggestions for the design of tight-binding, selective molecules.Keywords
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