Structure based development of novel specific inhibitors for cathepsin L and cathepsin S in vitro and in vivo

Specific inhibitors for cathepsin L and cathepsin S have been developed wit h the help of computer-graphic modeling based on the stereo-structure, The common fragment, N-(L- trans-carbamoyloxyrane-2-carbonyl)-phenylalanine-dim ethyl-amide, is required for specific inhibition of cathepsin L, Seven nove l inhibitors of the cathepsin L inhibitor Katunuma(CLIK) specifically inhib ited cathepsin L at a concentration of 10(-7) M in vitro, while almost no i nhibition of cathepsins B, C, S and IC was observed Four of the CLIKs are s table, and showed highly selective inhibition for hepatic cathepsin L in vi vo. One of the CLIK inhibitors contains an aldehyde group, and specifically Inhibits cathepsin S at 10(-7) M in vitro. (C) 1999 Federation of European Biochemical Societies.