Targeting telomerase and telomeres: a click chemistry approach towards highly selective G-quadruplex ligands.
Mol Biosyst
; 4(6): 629-42, 2008 Jun.
Article
en En
| MEDLINE
| ID: mdl-18493662
ABSTRACT
Maintenance of telomeres--specialized complexes that protect the ends of chromosomes, is undertaken by the enzyme complex telomerase, which is a key factor that is activated in more than 80% of cancer cells, but is absent in most normal cells. Targeting telomere maintenance mechanisms could potentially halt tumour growth across a broad spectrum of cancer types, with little cytotoxic effect outside cancer cells. Here, we describe in detail a new class of G-quadruplex binding ligands synthesized using a click chemistry approach. These ligands comprise a 1,3-di(1,2,3-triazol-4-yl)benzene pharmacophore, and display high levels of selectivity for interaction with G-quadruplex DNA vs. duplex DNA. The ability of these ligands to inhibit the enzymatic activity of telomerase correlates with their ability to stabilize quadruplex DNA, and with estimates of affinity calculated by molecular modeling.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Triazoles
/
Derivados del Benceno
/
ADN
/
Telómero
/
Telomerasa
/
G-Cuádruplex
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Mol Biosyst
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Año:
2008
Tipo del documento:
Article
País de afiliación:
Reino Unido