Anti-oligomerization sheet molecules: Design, synthesis and evaluation of inhibitory activities against α-synuclein aggregation.
Bioorg Med Chem
; 27(14): 3089-3096, 2019 07 15.
Article
en En
| MEDLINE
| ID: mdl-31196755
ABSTRACT
Aggregation of α-synuclein (α-Syn) play a key role in the development of Parkinson Disease (PD). One of the effective approaches is to stabilize the native, monomeric protein with suitable molecule ligands. We have designed and synthesized a series of sheet-like conjugated compounds which possess different skeletons and various heteroatoms in the two blocks located at both ends of linker, which have good π-electron delocalization and high ability of hydrogen-bond formation. They have shown anti-aggregation activities in vitro towards α-Syn with IC50 down to 1.09⯵M. The molecule is found binding in parallel to the NACore within NAC domain of α-Syn, interfering aggregation of NAC region within different α-Syn monomer, and further inhibiting or slowing down the formation of α-Syn oligomer nuclei at lag phase. The potential inhibitor obtained by our strategy is considered to be highly efficient to inhibit α-Syn aggregation.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Alfa-Sinucleína
/
Agregado de Proteínas
Límite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2019
Tipo del documento:
Article
País de afiliación:
China