Fragment-Based Deâ
Novo Design Reveals a Small-Molecule Inhibitor of Helicobacter Pylori HtrA.
Angew Chem Int Ed Engl
; 54(35): 10244-8, 2015 Aug 24.
Article
en En
| MEDLINE
| ID: mdl-26069090
ABSTRACT
Sustained identification of innovative chemical entities is key for the success of chemical biology and drug discovery. We report the fragment-based, computer-assisted deâ
novo design of a small molecule inhibiting Helicobacter pylori HtrA protease. Molecular binding of the designed compound to HtrA was confirmed through biophysical methods, supporting its functional activity in vitro. Hit expansion led to the identification of the currently best-in-class HtrA inhibitor. The results obtained reinforce the validity of ligand-based deâ
novo design and binding-kinetics-guided optimization for the efficient discovery of pioneering lead structures and prototyping drug-like chemical probes with tailored bioactivity.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Péptido Hidrolasas
/
Inhibidores de Proteasas
/
Proteínas Bacterianas
/
Diseño de Fármacos
/
Helicobacter pylori
/
Infecciones por Helicobacter
/
Bibliotecas de Moléculas Pequeñas
Límite:
Humans
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Año:
2015
Tipo del documento:
Article