Optimization of a series of dipeptides with a P3 threonine residue as non-covalent inhibitors of the chymotrypsin-like activity of the human 20S proteasome.
Bioorg Med Chem Lett
; 20(22): 6581-6, 2010 Nov 15.
Article
em En
| MEDLINE
| ID: mdl-20875739
ABSTRACT
Starting from a tripeptide screening hit, a series of dipeptide inhibitors of the proteasome with Thr as the P3 residue has been optimized with the aid of crystal structures in complex with the ß-5/6 active site of y20S. Derivative 25, (ß5 IC(50)=7.4 nM) inhibits only the chymotryptic activity of the proteasome, shows cellular activity against targets in the UPS, and inhibits proliferation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Treonina
/
Quimotripsina
/
Complexo de Endopeptidases do Proteassoma
/
Dipeptídeos
Limite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Ano de publicação:
2010
Tipo de documento:
Article