Dynamic Structures and Fast Transition Kinetics of Oxidized G-Quadruplexes.
Small
; 20(35): e2400485, 2024 Aug.
Article
en En
| MEDLINE
| ID: mdl-38678502
ABSTRACT
8-oxoguanines (8-oxoG) in cells form compromised G-quadruplexes (GQs), which may vary GQ mediated gene regulations. By mimicking molecularly crowded cellular environment using 40% DMSO or sucrose, here it is found that oxidized human telomeric GQs have stabilities close to the wild-type (WT) GQs. Surprisingly, while WT GQs show negative formation cooperativity between a Pt(II) binder and molecularly crowded environment, positive cooperativity is observed for oxidized GQ formation. Single-molecule mechanical unfolding reveals that 8-oxoG sequence formed more diverse and flexible structures with faster folding/unfolding transition kinetics, which facilitates the Pt(II) ligand to bind the best-fit structures with positive cooperativity. These findings offer new understanding on structures and properties of oxidized G-rich species in crowded environments. They also provide insights into the design of better ligands to target oxidized G-rich structures formed under oxidative cell stress.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Oxidación-Reducción
/
G-Cuádruplex
Límite:
Humans
Idioma:
En
Revista:
Small
/
Small (Weinh., Internet)
/
Small (Weinheim. Internet)
Asunto de la revista:
ENGENHARIA BIOMEDICA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos