Dynamic Structures and Fast Transition Kinetics of Oxidized G‐Quadruplexes

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. Su...

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Bibliographic Details
Published in:Small (Weinheim an der Bergstrasse, Germany) Germany), 2024-08, Vol.20 (35), p.e2400485-n/a
Main Authors: Ji, Jiahao, Sharma, Arpit, Pokhrel, Pravin, Karna, Deepak, Pandey, Shankar, Zheng, Yao‐Rong, Mao, Hanbin
Format: Article
Language:English
Subjects:
Cellular structure
cooperativity
flexible G‐rich structures
Flexible structures
folding/unfolding transition kinetics
Kinetics
Ligands
mechanical stability
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Summary: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. By mimicking molecularly crowded cellular environment, it is found that oxidized human telomeric G‐quadruplexes (GQs) have stabilities close to wild‐type (WT) GQs. Surprisingly, while WT GQs show negative formation cooperativity between a Pt(II) binder and crowded environment, positive cooperativity is observed for oxidized GQ formation. These observations can be rationalized by more diverse and flexible structures in oxidized GQs with faster folding/unfolding transition kinetics.
ISSN:1613-6810
1613-6829
1613-6829
DOI:10.1002/smll.202400485