Benzodioxocin-3-ones and N-acyl-3-amino-3-buten-2-ones: novel classes of cathepsin K cysteine protease inhibitors.
J Pept Res
; 63(3): 265-9, 2004 Mar.
Article
em En
| MEDLINE
| ID: mdl-15049838
ABSTRACT
The design, synthesis, enzymologic, and protein mass spectrometric characterization of benzodioxocin-3-one and N-acyl-3-amino-3-buten-2-one inhibitors of the cysteine protease cathepsin K are described. The benzodioxocin-3-one ring system is chemically unstable giving rise to a mixture of N-acyl-3-amino-3-buten-2-one and hemiketals. This mixture of N-acyl-3-amino-3-buten-2-one and hemiketals potently inhibits recombinant, human cathepsin K (IC50 = 36 nM) by a time-independent, irreversible mechanism. Formation of a covalent adduct between cathepsin K and inhibitor has been confirmed by mass spectrometry.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Catepsinas
/
Inibidores de Cisteína Proteinase
/
Cetonas
Idioma:
En
Revista:
J Pept Res
Assunto da revista:
BIOQUIMICA
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Estados Unidos