Selective recognition of c-MYC G-quadruplex DNA using prolinamide derivatives.
Org Biomol Chem
; 14(24): 5761-7, 2016 Jun 28.
Article
em En
| MEDLINE
| ID: mdl-26963597
ABSTRACT
Herein we report the design, synthesis, biophysical and biological evaluation of triazole containing prolinamide derivatives as selective c-MYC G-quadruplex binding ligands. A modular synthetic route has been devised for prolinamide derivatives using a copper(i) catalyzed azide-alkyne cycloaddition (CuAAC). The Förster resonance energy transfer (FRET) melting assay indicates that prolinamide trimers can significantly stabilize G-quadruplex structures over duplex DNA compared to prolinamide dimers. The fluorescent intercalator displacement (FID) assay shows that a trimer with prolinamide side chains at the para-position of the benzene ring can discriminate between different quadruplex structures and exhibits the highest binding affinity towards the c-MYC G-quadruplex structure. Molecular modeling studies reveal that the prolinamide trimer stacks upon the terminal G-quartet of the c-MYC G-quadruplex. Atomic force microscopy (AFM) analysis reveals that the tris-prolinamide ligand can be used to regulate the assembly of novel supramolecular nanoarchitectures. Further, in vitro cellular studies with human hepatocellular carcinoma (HepG2) cells indicate that the tris-prolinamide derivatives can inhibit cell proliferation and reduce c-MYC expression in cancer cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
DNA
/
Prolina
/
Proteínas Proto-Oncogênicas c-myc
/
Quadruplex G
Limite:
Humans
Idioma:
En
Revista:
Org Biomol Chem
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Índia