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"One Ring to Bind Them All"-Part II: Identification of Promising G-Quadruplex Ligands by Screening of Cyclophane-Type Macrocycles.

作者信息

Granzhan Anton, Monchaud David, Saettel Nicolas, Guédin Aurore, Mergny Jean-Louis, Teulade-Fichou Marie-Paule

机构信息

Section Recherche, Institut Curie, CNRS UMR176, Centre Universitaire Paris XI, Bat. 110, 91405 Orsay, France.

出版信息

J Nucleic Acids. 2010 May 9;2010:460561. doi: 10.4061/2010/460561.

DOI:10.4061/2010/460561
PMID:20725622
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2915812/
Abstract

A collection of 26 polyammonium cyclophane-type macrocycles with a large structural diversity has been screened for G-quadruplex recognition. A two-step selection procedure based on the FRET-melting assay was carried out enabling identification of macrocycles of high affinity (DeltaT(1/2) up to 30 degrees C) and high selectivity for the human telomeric G-quadruplex. The four selected hits possess sophisticated architectures, more particularly the presence of a pendant side-arm as well as the existence of a particular topological arrangement appear to be strong determinants of quadruplex binding. These compounds are thus likely to create multiple contacts with the target that may be at the origin of their high selectivity, thereby suggesting that this class of macrocycles offers unique advantages for targeting G-quadruplex-DNA.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a2/2915812/ca54e6b658bc/JNA2010-460561.008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a2/2915812/8853bdf93004/JNA2010-460561.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a2/2915812/f5ec161847bb/JNA2010-460561.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a2/2915812/f62b008a564d/JNA2010-460561.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a2/2915812/e18decc3255e/JNA2010-460561.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a2/2915812/5cfabb3ac747/JNA2010-460561.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a2/2915812/30b10f7fbad1/JNA2010-460561.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a2/2915812/7fcc5679fa78/JNA2010-460561.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a2/2915812/ca54e6b658bc/JNA2010-460561.008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a2/2915812/8853bdf93004/JNA2010-460561.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a2/2915812/f5ec161847bb/JNA2010-460561.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a2/2915812/f62b008a564d/JNA2010-460561.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a2/2915812/e18decc3255e/JNA2010-460561.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a2/2915812/5cfabb3ac747/JNA2010-460561.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a2/2915812/30b10f7fbad1/JNA2010-460561.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a2/2915812/7fcc5679fa78/JNA2010-460561.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a2/2915812/ca54e6b658bc/JNA2010-460561.008.jpg

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本文引用的文献

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The structures of quadruplex nucleic acids and their drug complexes.四链体核酸及其药物复合物的结构。
Curr Opin Struct Biol. 2009 Jun;19(3):239-50. doi: 10.1016/j.sbi.2009.04.001. Epub 2009 May 30.
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A fluorescent bisanthracene macrocycle discriminates between matched and mismatch-containing DNA.一种荧光双蒽大环化合物能够区分匹配的和含有错配的DNA。
通过 U 取代 DNA 中的配体敏化光化学生成反应探测 G-四链体结构。
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TWJ-Screen: an isothermal screening assay to assess ligand/DNA junction interactions in vitro.TWJ-Screen：一种用于体外评估配体/DNA 连接相互作用的等温筛选测定法。
Nucleic Acids Res. 2018 Feb 16;46(3):e16. doi: 10.1093/nar/gkx1118.
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Telomerase as a Cancer Target. Development of New Molecules.端粒酶作为癌症靶点：新型分子的研发
Curr Top Med Chem. 2016;16(22):2432-40. doi: 10.2174/1568026616666160212122425.
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