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核心技术专利：CN118964589B侵权必究
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基于亲和层析的用于筛选与 G-四链体结构选择性结合的潜在配体的方法。

Affinity Chromatography-Based Assays for the Screening of Potential Ligands Selective for G-Quadruplex Structures.

机构信息

Department of Chemical Sciences, University of Naples Federico II, via Cintia 21, 80126, Naples, Italy.

Institute of Biostructures and Bioimages, CNR, Via Tommaso De Amicis, 95, 80145, Naples, Italy.

出版信息

ChemistryOpen. 2022 May;11(5):e202200090. doi: 10.1002/open.202200090.

DOI:10.1002/open.202200090
PMID:35608081
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9127747/
Abstract

DNA G-quadruplexes (G4s) are key structures for the development of targeted anticancer therapies. In this context, ligands selectively interacting with G4s can represent valuable anticancer drugs. Aiming at speeding up the identification of G4-targeting synthetic or natural compounds, we developed an affinity chromatography-based assay, named G-quadruplex on Oligo Affinity Support (G4-OAS), by synthesizing G4-forming sequences on commercially available polystyrene OAS. Then, due to unspecific binding of several hydrophobic ligands on nude OAS, we moved to Controlled Pore Glass (CPG). We thus conceived an ad hoc functionalized, universal support on which both the on-support elongation and deprotection of the G4-forming oligonucleotides can be performed, along with the successive affinity chromatography-based assay, renamed as G-quadruplex on Controlled Pore Glass (G4-CPG) assay. Here we describe these assays and their applications to the screening of several libraries of chemically different putative G4 ligands. Finally, ongoing studies and outlook of our G4-CPG assay are reported.

摘要

DNA 四链体（G4s）是开发靶向抗癌疗法的关键结构。在这种情况下，与 G4 选择性相互作用的配体可以代表有价值的抗癌药物。为了加快鉴定靶向 G4 的合成或天然化合物，我们通过在商业可得的聚苯乙烯 OAS 上合成形成 G4 的序列，开发了一种基于亲和层析的测定法，命名为寡聚体亲和支持物上的 G-四链体（G4-OAS）。然后，由于许多疏水性配体在裸 OAS 上的非特异性结合，我们转向了可控孔玻璃（CPG）。因此，我们设计了一种专用的通用支持物，可在其上进行支持物上的延伸和 G4 形成寡核苷酸的脱保护，以及随后的基于亲和层析的测定法，重新命名为可控孔玻璃上的 G-四链体（G4-CPG）测定法。在这里，我们描述了这些测定法及其在筛选几种化学性质不同的潜在 G4 配体文库中的应用。最后，报告了我们的 G4-CPG 测定法的正在进行的研究和展望。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e64d/9127747/04902fb1b853/OPEN-11-e202200090-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e64d/9127747/d735a7d9ea48/OPEN-11-e202200090-g015.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e64d/9127747/2cb5e6991800/OPEN-11-e202200090-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e64d/9127747/444ee76902cb/OPEN-11-e202200090-g014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e64d/9127747/bda32ee02b28/OPEN-11-e202200090-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e64d/9127747/e8cea07b3d7f/OPEN-11-e202200090-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e64d/9127747/ae5b90985241/OPEN-11-e202200090-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e64d/9127747/b8e55e512161/OPEN-11-e202200090-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e64d/9127747/67f2892623b8/OPEN-11-e202200090-g017.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e64d/9127747/0c900139a7c9/OPEN-11-e202200090-g019.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e64d/9127747/5c20d909b487/OPEN-11-e202200090-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e64d/9127747/ece92ac80de2/OPEN-11-e202200090-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e64d/9127747/12419b4e897e/OPEN-11-e202200090-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e64d/9127747/04902fb1b853/OPEN-11-e202200090-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e64d/9127747/d735a7d9ea48/OPEN-11-e202200090-g015.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e64d/9127747/2cb5e6991800/OPEN-11-e202200090-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e64d/9127747/444ee76902cb/OPEN-11-e202200090-g014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e64d/9127747/bda32ee02b28/OPEN-11-e202200090-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e64d/9127747/e8cea07b3d7f/OPEN-11-e202200090-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e64d/9127747/ae5b90985241/OPEN-11-e202200090-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e64d/9127747/b8e55e512161/OPEN-11-e202200090-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e64d/9127747/67f2892623b8/OPEN-11-e202200090-g017.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e64d/9127747/0c900139a7c9/OPEN-11-e202200090-g019.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e64d/9127747/5c20d909b487/OPEN-11-e202200090-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e64d/9127747/ece92ac80de2/OPEN-11-e202200090-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e64d/9127747/12419b4e897e/OPEN-11-e202200090-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e64d/9127747/04902fb1b853/OPEN-11-e202200090-g010.jpg

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[4]
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[5]
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[6]
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本文引用的文献

[1]
Major Achievements in the Design of Quadruplex-Interactive Small Molecules.

Pharmaceuticals (Basel). 2022-2-28

[2]
Natural compounds from plants interacting with telomeric and oncogene G-quadruplex structures as potential anticancer agents.

Org Biomol Chem. 2021-11-25

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Identification of Effective Anticancer G-Quadruplex-Targeting Chemotypes through the Exploration of a High Diversity Library of Natural Compounds.

Pharmaceutics. 2021-10-3

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DNA Binding Mode Analysis of a Core-Extended Naphthalene Diimide as a Conformation-Sensitive Fluorescent Probe of G-Quadruplex Structures.

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The FDA-Approved Anthelmintic Pyrvinium Pamoate Inhibits Pancreatic Cancer Cells in Nutrient-Depleted Conditions by Targeting the Mitochondria.

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