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一种新型小分子，可改变端粒保护蛋白复合体的完整性并在端粒处引发DNA损伤反应。

A novel small molecule that alters shelterin integrity and triggers a DNA-damage response at telomeres.

作者信息

Rodriguez Raphaël, Müller Sebastian, Yeoman Justin A, Trentesaux Chantal, Riou Jean-François, Balasubramanian Shankar

机构信息

The University Chemical Laboratory, Lensfield Road, Cambridge, CB2 1EW, UK.

出版信息

J Am Chem Soc. 2008 Nov 26;130(47):15758-9. doi: 10.1021/ja805615w.

DOI:10.1021/ja805615w
PMID:18975896
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2746963/
Abstract

We describe a novel synthetic small molecule which shows an unprecedented stabilization of the human telomeric G-quadruplex with high selectivity relative to double-stranded DNA. We report that this compound can be used in vitro to inhibit telomerase activity and to uncap human POT1 (protection of telomeres 1) from the telomeric G-overhang. We also show that the small molecule G-quadruplex binder induces a partial alteration of shelterin through POT1 uncapping from telomeres in human HT1080 cancer cells and the presence of gammaH2AX foci colocalized at telomeres.

摘要

我们描述了一种新型合成小分子，它对人端粒G-四链体具有前所未有的稳定作用，相对于双链DNA具有高选择性。我们报告称，该化合物可在体外用于抑制端粒酶活性，并从端粒G-突出端解开人POT1（端粒保护蛋白1）。我们还表明，这种小分子G-四链体结合剂通过在人HT1080癌细胞中端粒的POT1解开以及端粒处共定位的γH2AX焦点的存在，诱导了端粒保护蛋白复合体的部分改变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ed3/2746963/c4dd891cc355/ukmss-27503-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ed3/2746963/2b5044d1b5b2/ukmss-27503-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ed3/2746963/c6eb5d3a04df/ukmss-27503-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ed3/2746963/c4dd891cc355/ukmss-27503-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ed3/2746963/2b5044d1b5b2/ukmss-27503-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ed3/2746963/c6eb5d3a04df/ukmss-27503-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ed3/2746963/c4dd891cc355/ukmss-27503-f0003.jpg

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本文引用的文献

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How shelterin protects mammalian telomeres.端粒保护蛋白复合体如何保护哺乳动物的端粒。
Annu Rev Genet. 2008;42:301-34. doi: 10.1146/annurev.genet.41.110306.130350.
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A platinum supramolecular square as an effective G-quadruplex binder and telomerase inhibitor.一种作为有效G-四链体结合剂和端粒酶抑制剂的铂超分子正方形。
化学修饰的CRISPR-Cas9能够靶向单个G-四链体和i-基序结构，揭示配体依赖性转录扰动。
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G-quadruplexes as potential traps for superenhancer marker BRD4: ligand-sensitive binding and co-separation in vitro.G-四链体作为超级增强子标记物BRD4的潜在捕获剂：体外配体敏感结合及共分离
Nucleic Acids Res. 2025 Jul 19;53(14). doi: 10.1093/nar/gkaf726.
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