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非经典病毒核酸结构的压力扰动研究

Pressure Perturbation Studies of Noncanonical Viral Nucleic Acid Structures.

作者信息

Somkuti Judit, Molnár Orsolya Réka, Grád Anna, Smeller László

机构信息

Department of Biophysics and Radiation Biology, Semmelweis University, 1094 Budapest, Hungary.

出版信息

Biology (Basel). 2021 Nov 12;10(11):1173. doi: 10.3390/biology10111173.

Abstract

G-quadruplexes are noncanonical structures formed by guanine-rich sequences of the genome. They are found in crucial loci of the human genome, they take part in the regulation of important processes like cell proliferation and cell death. Much less is known about the subjects of this work, the viral G-quadruplexes. We have chosen three potentially G-quadruplex-forming sequences of hepatitis B. We measured the stability and the thermodynamic parameters of these quadruplexes. We also investigated the potential stabilization of these G-quadruplexes by binding a special ligand that was originally developed for cancer therapy. Fluorescence and infrared spectroscopic measurements were performed over wide temperature and pressure ranges. Our experiments indicate the small unfolding volume change of all three oligos. We found a difference between the unfolding of the 2-quartet and the 3-quartet G-quadruplexes. All three G-quadruplexes were stabilized by TMPyP4, which is a cationic porphyrin developed for stabilizing the human telomere.

摘要

G-四链体是由基因组中富含鸟嘌呤的序列形成的非经典结构。它们存在于人类基因组的关键位点,参与细胞增殖和细胞死亡等重要过程的调控。对于这项工作的研究对象——病毒G-四链体,人们了解得要少得多。我们选择了乙肝病毒三个潜在的可形成G-四链体的序列。我们测量了这些四链体的稳定性和热力学参数。我们还通过结合一种最初为癌症治疗而开发的特殊配体,研究了这些G-四链体的潜在稳定性增强情况。在很宽的温度和压力范围内进行了荧光和红外光谱测量。我们的实验表明,所有三种寡核苷酸的解折叠体积变化都很小。我们发现二联体和三联体G-四链体的解折叠存在差异。所有三种G-四链体都被TMPyP4稳定,TMPyP4是一种为稳定人类端粒而开发的阳离子卟啉。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3882/8615049/56c14f5e6225/biology-10-01173-g001.jpg

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