Peptide ketobenzoxazole inhibitors bound to cathepsin K.

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

Biochemistry

journal_title

Biochemistry

authors

McGrath ME,Sprengeler PA,Hill CM,Martichonok V,Cheung H,Somoza JR,Palmer JT,Janc JW

doi

10.1021/bi035041x

subject

Has Abstract

pub_date

2003-12-30 00:00:00

pages

15018-28

issue

51

eissn

0006-2960

issn

1520-4995

journal_volume

42

pub_type

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