Selective inhibition of the immunoproteasome by ligand-induced crosslinking of the active site.
Angew Chem Int Ed Engl
; 53(44): 11969-73, 2014 Oct 27.
Article
en En
| MEDLINE
| ID: mdl-25244435
ABSTRACT
The concept of proteasome inhibition ranks among the latest achievements in the treatment of blood cancer and represents a promising strategy for modulating autoimmune diseases. In this study, we describe peptidic sulfonyl fluoride inhibitors that selectively block the catalytic ß5 subunit of the immunoproteasome by inducing only marginal cytotoxic effects. Structural and mass spectrometric analyses revealed a novel reaction mechanism involving polarity inversion and irreversible crosslinking of the proteasomal active site. We thus identified the sulfonyl fluoride headgroup for the development and optimization of immunoproteasome selective compounds and their possible application in autoimmune disorders.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Complejo de la Endopetidasa Proteasomal
/
Inhibidores de Proteasoma
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Año:
2014
Tipo del documento:
Article