Discovery of a potent and highly ß1 specific proteasome inhibitor from a focused library of urea-containing peptide vinyl sulfones and peptide epoxyketones.
Org Biomol Chem
; 10(1): 181-94, 2012 Jan 07.
Article
em En
| MEDLINE
| ID: mdl-22105930
ABSTRACT
Syringolins, a class of natural products, potently and selectively inhibit the proteasome and show promising antitumour activity. To gain insight in the mode of action of syringolins, the ureido structural element present in syringolins is incorporated in oligopeptide vinyl sulfones and peptide epoxyketones yielding a focused library of potent new proteasome inhibitors. The distance of the ureido linkage with respect to the electrophilic trap strongly influences subunit selectivity within the proteasome. Compounds 13 and 15 are ß5 selective and their potency exceeds that of syringolin A. In contrast, 5 may well be the most potent ß1 selective compound active in living cells reported to date.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Sulfonas
/
Ureia
/
Inibidores de Proteassoma
/
Cetonas
Limite:
Humans
Idioma:
En
Revista:
Org Biomol Chem
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Holanda