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不同长度序列的启动子 G-四链体：物理化学研究。

Promoter G-Quadruplexes from Sequences of Different Length: A Physicochemical Study.

机构信息

Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49, 80131 Naples, Italy.

Department of Chemical Sciences, University of Naples Federico II, Via Cintia 4, 80126 Naples, Italy.

出版信息

Int J Mol Sci. 2021 Jan 5;22(1):448. doi: 10.3390/ijms22010448.

DOI:10.3390/ijms22010448
PMID:33466280
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7795837/
Abstract

DNA G-quadruplexes (G4s) form in relevant genomic regions and intervene in several biological processes, including the modulation of oncogenes expression, and are potential anticancer drug targets. The human proto-oncogene promoter region contains guanine-rich sequences able to fold into G4 structures. Here, by using circular dichroism and differential scanning calorimetry as complementary physicochemical methodologies, we compared the thermodynamic stability of the G4s formed by a shorter and a longer version of the promoter sequence, namely 5'-AGGGCGGTGTGGGAATAGGGAA-3' ( 22RT) and 5'-AGGGCGGTGTGGGAAGAGGGAAGAGGGGGAGG-3' ( 32R). Our results show that the unfolding mechanism of 32R is more complex than that of 22RT. The different thermodynamic stability is discussed based on the recently determined NMR structures. The binding properties of TMPyP4 and BRACO-19, two well-known G4-targeting anticancer compounds, to the G4s were also investigated. The present physicochemical study aims to help in choosing the best G4 target for potential anticancer drugs.

摘要

DNA 四链体（G4s）在相关的基因组区域形成，参与多种生物学过程，包括调节癌基因的表达，是潜在的抗癌药物靶点。人类原癌基因启动子区域含有能够折叠成 G4 结构的富含鸟嘌呤的序列。在这里，我们使用圆二色性和差示扫描量热法作为互补的物理化学方法，比较了较短和较长版本的启动子序列形成的 G4s 的热力学稳定性，即 5'-AGGGCGGTGTGGGAATAGGGAA-3'（22RT）和 5'-AGGGCGGTGTGGGAAGAGGGAAGAGGGGGAGG-3'（32R）。我们的结果表明，32R 的解折叠机制比 22RT 更复杂。基于最近确定的 NMR 结构，讨论了不同的热力学稳定性。还研究了两种著名的 G4 靶向抗癌化合物 TMPyP4 和 BRACO-19 与 G4s 的结合特性。本物理化学研究旨在帮助选择最佳的 G4 靶点用于潜在的抗癌药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20e9/7795837/f3550d2e75b0/ijms-22-00448-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20e9/7795837/e7e111aab680/ijms-22-00448-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20e9/7795837/f3550d2e75b0/ijms-22-00448-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20e9/7795837/e7e111aab680/ijms-22-00448-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20e9/7795837/7a5673fb9dcc/ijms-22-00448-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20e9/7795837/6fbf0624a892/ijms-22-00448-g003.jpg
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