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 alpha-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.
journal_name
Biochemistryjournal_title
Biochemistryauthors
McGrath ME,Sprengeler PA,Hill CM,Martichonok V,Cheung H,Somoza JR,Palmer JT,Janc JWdoi
10.1021/bi035041xsubject
Has Abstractpub_date
2003-12-30 00:00:00pages
15018-28issue
51eissn
0006-2960issn
1520-4995journal_volume
42pub_type
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