人类端粒g -四重体与负电荷稳定剂之间选择性结合的分子洞察。

IF 2.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Zhiguo Wang, Jianfeng Li, Jun Liu, Lihui Wang, Yanhua Lu, Jun-Ping Liu
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引用次数: 7

摘要

人类端粒单链悬垂在生理条件下形成称为g -四重体(G4)的分子内高阶结构。端粒G4稳定可以防止端粒酶在癌细胞中延长端粒,这是一种很有前途的癌症治疗策略。利用分子对接和分子动力学(MD)模拟,在原子水平上研究了阴离子酞菁3,4',4',4' -四磺酸(APC)与人杂合体(3 + 1)G4s的特异性结合。我们发现APC更倾向于与端粒杂化型II (hybrid-II) G4的端层结合,而与杂化型I (hybrid-I) G4的凹槽结合具有显著的稳定效果和更有利的结合自由能。非共价相互作用分析和结合自由能分解表明,范德华相互作用在APC与端粒杂化G4s的结合中起主导作用。这些发现首次为揭示选择性端粒G4稳定剂的设计提供了证据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Molecular insight into the selective binding between human telomere G-quadruplex and a negatively charged stabilizer.

The single-strand human telomere overhang forms intramolecular high-order structures named G-quadruplex (G4) under physiological conditions. Telomere G4 stabilization prevents telomere lengthening by telomerase in cancer cells representing a promising strategy in cancer therapy. Using molecular docking and molecular dynamics (MD) simulations, specific binding of the anionic phthalocyanine 3,4',4'',4'''-tetrasulfonic acid (APC) to the human hybrid (3 + 1) G4s was investigated at the atomic level. We found that APC preferred the end-stacking binding with the telomere hybrid type II (hybrid-II) G4 as compared to the groove binding with the hybrid type I (hybrid-I) G4 remarkable stabilizing effect and more favourable binding free energies. Analysis of non-covalent interaction and decomposition of the binding free energy revealed that van der Waals interaction played a leading role in the binding of APC and telomere hybrid G4s. These findings provide evidence for the first time to shed light on the designs of selective telomere G4 stabilizers.

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来源期刊
Clinical and Experimental Pharmacology and Physiology
Clinical and Experimental Pharmacology and Physiology PHARMACOLOGY & PHARMACY-PHYSIOLOGY
自引率
0.00%
发文量
128
期刊介绍: Clinical and Experimental Pharmacology and Physiology is an international journal founded in 1974 by Mike Rand, Austin Doyle, John Coghlan and Paul Korner. Our focus is new frontiers in physiology and pharmacology, emphasizing the translation of basic research to clinical practice. We publish original articles, invited reviews and our exciting, cutting-edge Frontiers-in-Research series’.
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