Design and synthesis of dipeptide nitriles as reversible and potent Cathepsin S inhibitors.
J Med Chem
; 45(25): 5471-82, 2002 Dec 05.
Article
em En
| MEDLINE
| ID: mdl-12459015
ABSTRACT
The specificity of the immune response relies on processing of foreign proteins and presentation of antigenic peptides at the cell surface. Inhibition of antigen presentation, and the subsequent activation of T-cells, should, in theory, modulate the immune response. The cysteine protease Cathepsin S performs a fundamental step in antigen presentation and therefore represents an attractive target for inhibition. Herein, we report a series of potent and reversible Cathepsin S inhibitors based on dipeptide nitriles. These inhibitors show nanomolar inhibition of the target enzyme as well as cellular potency in a human B cell line. The first X-ray crystal structure of a reversible inhibitor cocrystallized with Cathepsin S is also reported.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Catepsinas
/
Dipeptídeos
/
Inibidores Enzimáticos
/
Nitrilas
Limite:
Humans
Idioma:
En
Revista:
J Med Chem
Assunto da revista:
QUIMICA
Ano de publicação:
2002
Tipo de documento:
Article
País de afiliação:
Estados Unidos