期刊
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
卷 166, 期 -, 页码 1320-1334出版社
ELSEVIER
DOI: 10.1016/j.ijbiomac.2020.11.013
关键词
Higher-order G-quadruplex; G-quadruplex multimer; Telomere; Naphthalene diimide; G4-CPG assay
资金
- FIRC-AIRC fellowship for Italy
- Regione Campania-POR Campania FESR 2014/2020 [B61G18000470007]
NDI-5 has shown promising potential as a ligand for multimeric G4 structures, selectively targeting them over duplex DNA. Experimental analyses including CD, gel electrophoresis, ITC, and fluorescence spectroscopy suggest that NDI-5 effectively binds and stabilizes tel46 G4, favoring a hybrid folding in K+-containing buffer.
To selectively target telomeric G-quadruplex (G4) DNA, monomeric and dimeric naphthalene diimides (NDIs) were investigated as binders of multimeric G4 structures able to discriminate duplex DNA. These NDIs were analysed by the affinity chromatography-based screening G4-CPG (G-quadruplex on Controlled Pore Glass), using the sequence d[AGGG(TTAGGG)7] (tel46), folding into two consecutive G4s, as model of the human telomeric G4 multimer. In parallel, a telomeric G4 monomer (tel26) and a duplex structure (ds27) were used as controls. According to G4-CPG screening, NDI-5 proved to be the best ligand in terms of dimeric G4 vs. duplex DNA selectivity andwas analysed by circular dichroism(CD), gel electrophoresis, isothermal titration calorimetry (ITC) and fluorescence spectroscopy in its interactions with tel46. NDI-5 strongly binds and stabilizes tel46 G4, favouring a hybrid folding in K+-containing buffer. Under these conditions, the binding process comprises a first event involving three molecules of NDI-5 and a second one in which other six molecules bind to the DNA. In ametal cation-free system, NDI-5 induces tel46 G4 folding, as indicated by CD and PAGE, favouring an antiparallel structuring. Docking simulations showed that NDI-5 can effectively bind to the pocket between two G4 units, representing a promising ligand for multimeric G4s. (c) 2020 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据