Synthesis of quinolinium-based probes and studies of their effects for selective G-quadruplex DNA targeting

Two quinolinium conjugates as G-quadruplex probes were presented. The binding properties and mechanism were investigated using both experimental and docking studies.

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Exploring the Interaction of Curaxin CBL0137 with G-Quadruplex DNA Oligomers

International Journal of Molecular Sciences ◽

10.3390/ijms22126476 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6476

Author(s):

Sabrina Dallavalle ◽

Luce M. Mattio ◽

Roberto Artali ◽

Loana Musso ◽

Anna Aviñó ◽

...

Keyword(s):

Dna Binding ◽

31P Nmr ◽

Antitumor Activities ◽

Binding Properties ◽

Dna Oligomers ◽

Quadruplex Dna ◽

Dna Targeting ◽

G Quadruplex ◽

Dna Binding Properties ◽

Insight Into

Curaxins and especially the second-generation derivative curaxin CBL0137 have important antitumor activities in multiple cancers such as glioblastoma, melanoma and others. Although most of the authors suggest that their mechanism of action comes from the activation of p53 and inactivation of NF-kB by targeting FACT, there is evidence supporting the involvement of DNA binding in their antitumor activity. In this work, the DNA binding properties of curaxin CBL0137 with model quadruplex DNA oligomers were studied by 1H NMR, CD, fluorescence and molecular modeling. We provided molecular details of the interaction of curaxin with two G-quadruplex structures, the single repeat of human telomere d(TTAGGGT)4 and the c-myc promoter Pu22 sequence. We also performed 1H and 31P NMR experiments were also performed in order to investigate the interaction with duplex DNA models. Our data support the hypothesis that the interaction of curaxin with G-quadruplex may provide a novel insight into the DNA-binding properties of CBL0137, and it will be helpful for the design of novel selective DNA-targeting curaxin analogues.

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G-quadruplex binding properties of a potent PARP-1 inhibitor derived from 7-azaindole-1-carboxamide

Scientific Reports ◽

10.1038/s41598-021-83474-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Sabrina Dallavalle ◽

Loana Musso ◽

Roberto Artali ◽

Anna Aviñó ◽

Leonardo Scaglioni ◽

...

Keyword(s):

Therapeutic Potential ◽

Parp Inhibition ◽

Inhibition Mechanism ◽

Binding Properties ◽

Dna Oligomers ◽

Quadruplex Dna ◽

G Quadruplex ◽

Molecular Bases ◽

Dna Binding Properties ◽

Parp 1

AbstractPoly ADP-ribose polymerases (PARP) are key proteins involved in DNA repair, maintenance as well as regulation of programmed cell death. For this reason they are important therapeutic targets for cancer treatment. Recent studies have revealed a close interplay between PARP1 recruitment and G-quadruplex stabilization, showing that PARP enzymes are activated upon treatment with a G4 ligand. In this work the DNA binding properties of a PARP-1 inhibitor derived from 7-azaindole-1-carboxamide, (2-[6-(4-pyrrolidin-1-ylmethyl-phenyl)-pyrrolo[2,3-b]pyridin-1-yl]-acetamide, compound 1) with model duplex and quadruplex DNA oligomers were studied by NMR, CD, fluorescence and molecular modelling. We provide evidence that compound 1 is a strong G-quadruplex binder. In addition we provide molecular details of the interaction of compound 1 with two model G-quadruplex structures: the single repeat of human telomeres, d(TTAGGGT)4, and the c-MYC promoter Pu22 sequence. The formation of defined and strong complexes with G-quadruplex models suggests a dual G4 stabilization/PARP inhibition mechanism of action for compound 1 and provides the molecular bases of its therapeutic potential.

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N-methyl mesoporphyrin IX as a highly selective light-up probe for G-quadruplex DNA

Journal of Porphyrins and Phthalocyanines ◽

10.1142/s1088424619300179 ◽

2019 ◽

Vol 23 (11n12) ◽

pp. 1195-1215 ◽

Cited By ~ 5

Author(s):

Ariana Yett ◽

Linda Yingqi Lin ◽

Dana Beseiso ◽

Joanne Miao ◽

Liliya A. Yatsunyk

Keyword(s):

Optical Properties ◽

Small Molecules ◽

Genomic Stability ◽

Water Soluble ◽

Biological Processes ◽

Binding Properties ◽

Quadruplex Dna ◽

Dna Structures ◽

G Quadruplex ◽

High Fluorescence

[Formula: see text]-methyl mesoporphyrin IX (NMM) is a water-soluble, non-symmetric porphyrin with excellent optical properties and unparalleled selectivity for G-quadruplex (GQ) DNA. G-quadruplexes are non-canonical DNA structures formed by guanine-rich sequences. They are implicated in genomic stability, longevity, and cancer. The ability of NMM to selectively recognize GQ structures makes it a valuable scaffold for designing novel GQ binders. In this review, we survey the literature describing the GQ-binding properties of NMM as well as its wide utility in chemistry and biology. We start with the discovery of the GQ-binding properties of NMM and the development of NMM-binding aptamers. We then discuss the optical properties of NMM, focusing on the light-switch effect — high fluorescence of NMM induced upon its binding to GQ DNA. Additionally, we examine the affinity and selectivity of NMM for GQs, as well as its ability to stabilize GQ structures and favor parallel GQ conformations. Furthermore, a portion of the review is dedicated to the applications of NMM-GQ complexes as biosensors for heavy metals, small molecules ([Formula: see text] ATP and pesticides), DNA, and proteins. Finally and importantly, we discuss the utility of NMM as a probe to investigate the roles of GQs in biological processes.

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Synthesis, docking studies and antitumor activity of phenanthroimidazole derivatives as promising c-myc G-quadruplex DNA stabilizers

Bioorganic Chemistry ◽

10.1016/j.bioorg.2020.104074 ◽

2020 ◽

Vol 102 ◽

pp. 104074

Author(s):

Qiong Wu ◽

Yue Song ◽

Ruotong Liu ◽

Rui Wang ◽

Wenjie Mei ◽

...

Keyword(s):

Antitumor Activity ◽

Docking Studies ◽

Quadruplex Dna ◽

G Quadruplex

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Biophysical probing of the binding properties of a Cu(II) complex with G-quadruplex DNA: an experimental and computational study

Luminescence ◽

10.1002/bio.2916 ◽

2015 ◽

Vol 31 (1) ◽

pp. 22-29 ◽

Cited By ~ 5

Author(s):

Mohammad Reza Housaindokht ◽

Asma Verdian-Doghaei

Keyword(s):

Computational Study ◽

Binding Properties ◽

Quadruplex Dna ◽

G Quadruplex

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Spectroscopic Studies on the Binding Properties of Ofloxacin and Human Telomeric G-Quadruplex DNA

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.634-638.1062 ◽

2013 ◽

Vol 634-638 ◽

pp. 1062-1065 ◽

Cited By ~ 1

Author(s):

Xu Jian Luo ◽

Qi Pin Qin ◽

Yu Lan Li ◽

Yan Yang

Keyword(s):

Spectral Analysis ◽

Fluorescence Emission ◽

Spectroscopic Studies ◽

Binding Properties ◽

Quadruplex Dna ◽

G4 Dna ◽

G Quadruplex ◽

Shoulder Peak ◽

Binding Intensity ◽

Dna Complex

The binding of ofloxacin with human telomeric G-quadruplex DNA, Htel-G4-DNA and Htel-3-G4-DNA were examined by Fluorescence and CD spectroscopic methods. In the Fluorescence emission spectral analysis, the addition of ofloxacin induced significant quenching on the fluorescence emission of TO-G4-DNA complex. The fluorescence spectral analysis indicated that ofloxacin exhibited higher binding affinity and binding intensity to Htel-G4-DNA than Htel-3-G4-DNA. In the CD spectral analysis, the interaction with ofloxacin did not disturb the characteristic absorption of Htel-G4-DNA at 290 nm corresponding to its antiparallel form, and only slightly increased the positive absorption at 270 nm as shoulder peak, which suggests the antiparallel structure of G-quadruplex can remain stable in the presence of ofloxacin

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Studies on the Material Properties of Platinum Complex Binding to Human Telomeric G-Quadruplex DNA

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.700.63 ◽

2013 ◽

Vol 700 ◽

pp. 63-66

Author(s):

Xu Jian Luo ◽

Qi Pin Qin ◽

Yu Lan Li ◽

Yan Cheng Liu

Keyword(s):

Binding Affinity ◽

Material Properties ◽

Platinum Complex ◽

Spectroscopic Methods ◽

Binding Properties ◽

Quadruplex Dna ◽

G Quadruplex ◽

New Material ◽

Binding Intensity ◽

Ct Dna

A new material of cation platinum (II) complex has been synthesized and characterized. The new material binding properties with human telomeric G-quadruplex DNA (G4-Htel DNA) and ct-DNA were examined by UV-Vis and CD spectroscopic methods. The results showed that complex exhibited higher binding affinity and binding intensity to G4-Htel DNA (up to Kb = 1.54×106 M-1) and with selectivity (up to 11-fold) over duplex DNA. The CD results suggests the antiparallel structure of G-quadruplex can remain stable in the presence of platinum complex and the complex may bind to DNA by intercalation mode.

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