Molecular mechanism of anionic stabilizer for telomere G-quadruplex

Zhiguo Wang; Jianfeng Li; Jun Liu; Lihui Wang; Yanhua Lu; Jun-Ping Liu

doi:10.52601/bpr.2022.220039

Volume 8 Issue 4

Aug. 2022

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Article Navigation > Biophysics Reports > 2022 > 8(4): 225-238

Zhiguo Wang, Jianfeng Li, Jun Liu, Lihui Wang, Yanhua Lu, Jun-Ping Liu. Molecular mechanism of anionic stabilizer for telomere G-quadruplex[J]. Biophysics Reports, 2022, 8(4): 225-238. doi: 10.52601/bpr.2022.220039

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Zhiguo Wang, Jianfeng Li, Jun Liu, Lihui Wang, Yanhua Lu, Jun-Ping Liu. Molecular mechanism of anionic stabilizer for telomere G-quadruplex[J]. Biophysics Reports, 2022, 8(4): 225-238. doi: 10.52601/bpr.2022.220039

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Molecular mechanism of anionic stabilizer for telomere G-quadruplex

doi: 10.52601/bpr.2022.220039

Zhiguo Wang^{1
,
,},
Jianfeng Li¹,
Jun Liu¹,
Lihui Wang¹,
Yanhua Lu¹,
Jun-Ping Liu^{1, 2, 3, 4
,
,}

1.
Institute of Ageing Research, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou 311121, China
2.
Department of Immunology, Central Eastern Clinical School, Monash University, Melbourne, Vitoria 3004, Australia
3.
Hudson Institute of Medical Research, Clayton, Victoria 3168, Australia
4.
Department of Molecular and Translational Science, Monash University, Clayton, Victoria 3168, Australia

More Information

Corresponding author: zhgwang@hznu.edu.cn (Z. Wang); jun-ping.liu@hznu.edu.cn (J.-P. Liu)
Received Date: 10 August 2021
Accepted Date: 19 July 2022

Available Online: 08 November 2022

Publish Date: 31 August 2022

Abstract

Abstract

Telomere DNA assumes a high-order G-quadruplex (G4) structure, stabilization of which prevents telomere lengthening by telomerase in cancer. Through applying combined molecular simulation methods, an investigation on the selective binding mechanism of anionic phthalocyanine 3,4ʹ,4ʹʹ,4ʹʹʹ-tetrasulfonic acid (APC) and human hybrid (3 + 1) G4s was firstly performed at the atomic level. Compared to the groove binding mode of APC and the hybrid type I (hybrid-I) telomere G4, APC preferred to bind to the hybrid type II (hybrid-II) telomere G4 via end-stacking interactions, which showed much more favorable binding free energies. Analyses of the non-covalent interaction and binding free energy decomposition revealed a decisive role of van der Waals interaction in the binding of APC and telomere hybrid G4s. And the binding of APC and hybrid-II G4 that showed the highest binding affinity adopted the end-stacking binding mode to form the most extensive van der Waals interactions. These findings add new knowledge to the design of selective stabilizers targeting telomere G4 in cancer.
- Telomere G-quadruplex,
- Anionic stabilizer,
- Selective mechanism,
- Molecular dynamics,
- MM/GBSA

Zhiguo Wang, Jianfeng Li, Jun Liu, Lihui Wang, Yanhua Lu, and Jun-Ping Liu declare that they have no conflict of interest.
This article does not contain any studies with human or animal subjects performed by any of the authors.

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