Premium
Structure based development of novel specific inhibitors for cathepsin L and cathepsin S in vitro and in vivo
Author(s) -
Katunuma N.,
Murata E.,
Kakegawa H.,
Matsui A.,
Tsuzuki H.,
Tsuge H.,
Turk D.,
Turk V.,
Fukushima M.,
Tada Y.,
Asao T.
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)01107-2
Subject(s) - cathepsin o , cathepsin , cathepsin a , in vivo , cathepsin l1 , in vitro , cathepsin b , chemistry , cathepsin d , biochemistry , cathepsin l , cathepsin s , microbiology and biotechnology , enzyme , biology
Specific inhibitors for cathepsin L and cathepsin S have been developed with the help of computer‐graphic modeling based on the stereo‐structure. The common fragment, N ‐( L ‐ trans ‐carbamoyloxyrane‐2‐carbonyl)‐phenylalanine‐dimethylamide, is required for specific inhibition of cathepsin L. Seven novel inhibitors of the cathepsin L inhibitor Katunuma (CLIK) specifically inhibited cathepsin L at a concentration of 10 −7 M in vitro, while almost no inhibition of cathepsins B, C, S and K was observed. Four of the CLIKs are stable, and showed highly selective inhibition for hepatic cathepsin L in vivo. One of the CLIK inhibitors contains an aldehyde group, and specifically inhibits cathepsin S at 10 −7 M in vitro.