Peptidyl fluoromethyl ketones as inhibitors of cathepsin B. Implication for treatment of rheumatoid arthritis.
Biochem Pharmacol
; 44(6): 1201-7, 1992 Sep 25.
Article
en En
| MEDLINE
| ID: mdl-1417942
ABSTRACT
Peptidyl fluoromethyl ketones (FMKs), with the amino acid sequence Phe-Ala held constant but with variable N-terminal groups, were synthesized and tested for inhibition of the cysteine proteinase cathepsin B. The FMKs were effective in inhibiting cathepsin B activity in vitro. The inhibition was time dependent and was not reversed by dialysis, suggesting covalent modification of the enzyme. Cathepsin B activity present in livers and kidneys of rats treated with FMKs was reduced by 22-91% 4 hr after a single oral dose of 25 mg/kg. The FMKs inhibited the severity of inflammation and the extent of cartilage and bone damage in adjuvant-induced arthritis. These effects were seen during the late-stage of the disease with no effect on onset or incidence of disease. This is consistent with inhibition of protease-mediated damage. These FMKs or derivatives may be of clinical value in the treatment of arthritis.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Catepsina B
/
Dipéptidos
/
Cetonas
/
Riñón
/
Hígado
Límite:
Animals
Idioma:
En
Revista:
Biochem Pharmacol
Año:
1992
Tipo del documento:
Article