Design, solid-phase synthesis, and evaluation of a phenyl-piperazine-triazine scaffold as α-helix mimetics.
ACS Comb Sci
; 16(12): 695-701, 2014 Dec 08.
Article
en En
| MEDLINE
| ID: mdl-25336412
ABSTRACT
α-Helices play a critical role in mediating many protein-protein interactions (PPIs) as recognition motifs. Therefore, there is a considerable interest in developing small molecules that can mimic helical peptide segments to modulate α-helix-mediated PPIs. Due to the relatively low aqueous solubility and synthetic difficulty of most current α-helix mimetic small molecules, one important goal in this area is to develop small molecules with favorable physicochemical properties and ease of synthesis. Here we designed phenyl-piperazine-triazine-based α-helix mimetics that possess improved water solubility and excellent synthetic accessibility. We developed a facile solid-phase synthetic route that allows for rapid creation of a large, diverse combinatorial library of α-helix mimetics. Further, we identified a selective inhibitor of the Mcl-1/BH3 interaction by screening a focused library of phenyl-piperazine-triazines, demonstrating that the scaffold is able to serve as functional mimetics of α-helical peptides. We believe that our phenyl-piperazine-triazine-based α-helix mimetics, along with the facile and divergent solid-phase synthetic method, have great potential as powerful tools for discovering potent inhibitors of given α-helix-mediated PPIs.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Piperazinas
/
Triazinas
/
Benzoatos
/
Biomimética
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
ACS Comb Sci
Año:
2014
Tipo del documento:
Article
País de afiliación:
Corea del Sur