Studies on the binding of 5-N-methylated quindoline derivative to human telomeric G-quadruplex.
Biochem Biophys Res Commun
; 406(3): 454-8, 2011 Mar 18.
Article
en En
| MEDLINE
| ID: mdl-21333628
Quindoline derivatives as telomeric quadruplex ligands have shown good biological activity for telomerase inhibition. In the present study, we used spectroscopic and calorimetric methods to investigate the interactions between a quindoline derivative (5-methyl-11-(2-morpholinoethylamino)-10-H-indolo-[3,2-b]quinolin-5-ium iodide, compound 1) and human telomeric G-quadruplex. The thermodynamic studies using isothermal titration calorimetry (ITC) indicated that their binding process was temperature-dependent and enthalpy-entropy co-driven. The significant negative heat capacity was obtained experimentally from the temperature dependence of enthalpy changes, which was consistent with that from theoretical calculation, and all suggesting significant hydrophobic contribution to the molecular recognition process. Based on the results from UV-vis, ITC, steady-state and time-resolved fluorescence, their binding mode was determined as two ligand molecules stacking on the quartets on both ends of the quadruplex. These results shed light on rational design and development of quindoline derivatives as G-quadruplex binding ligands.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Quinolinas
/
Compuestos de Quinolinio
/
Telómero
/
Alcaloides
/
G-Cuádruplex
/
Indoles
Límite:
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2011
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Estados Unidos