Selectivity profiling of DegP substrates and inhibitors.
Bioorg Med Chem
; 17(7): 2920-4, 2009 Apr 01.
Article
en En
| MEDLINE
| ID: mdl-19233659
ABSTRACT
Protein quality control factors are involved in many key physiological processes and severe human diseases that are based on misfolding or amyloid formation. Prokaryotic representatives are often virulence factors of pathogenic bacteria. Therefore, protein quality control factors represent a novel class of drug targets. The bacterial serine protease DegP, belonging to the widely conserved family of HtrA proteases, exhibits unusual structural and functional plasticity that could be exploited by small molecule modulators. However, only one weak synthetic peptide substrate and no inhibitors are available to date. We report the identification of a potent heptameric pNA-substrate and chloromethyl ketone based inhibitors of DegP. In addition, specificity profiling resulted in the identification of one strong inhibitor and a potent substrate for subtilisin as well as a number of specific elastase substrates and inhibitors.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Péptidos
/
Inhibidores de Proteasas
/
Serina Endopeptidasas
/
Proteínas Periplasmáticas
/
Clorometilcetonas de Aminoácidos
/
Proteínas de Choque Térmico
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Bioorg Med Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2009
Tipo del documento:
Article
País de afiliación:
Alemania