Dynamic Structures and Fast Transition Kinetics of Oxidized G-Quadruplexes.
Small
; 20(35): e2400485, 2024 Aug.
Article
em 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.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Oxirredução
/
Quadruplex G
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article