scholarly journals “One Ring to Bind Them All”—Part I: The Efficiency of the Macrocyclic Scaffold for G-Quadruplex DNA Recognition

2010 ◽  
Vol 2010 ◽  
pp. 1-19 ◽  
Author(s):  
David Monchaud ◽  
Anton Granzhan ◽  
Nicolas Saettel ◽  
Aurore Guédin ◽  
Jean-Louis Mergny ◽  
...  
Keyword(s):  
State Of The Art ◽  
Biological Activities ◽  
Dna Recognition ◽  
Dna Conformation ◽  
Binding Properties ◽  
Quadruplex Dna ◽  
Current State ◽  
G Quadruplex ◽  
Biological Aspects

Macrocyclic scaffolds are particularly attractive for designing selective G-quadruplex ligands essentially because, on one hand, they show a poor affinity for the “standard” B-DNA conformation and, on the other hand, they fit nicely with the external G-quartets of quadruplexes. Stimulated by the pioneering studies on the cationic porphyrin TMPyP4 and the natural product telomestatin, follow-up studies have developed, rapidly leading to a large diversity of macrocyclic structures with remarkable-quadruplex binding properties and biological activities. In this review we summarize the current state of the art in detailing the three main categories of quadruplex-binding macrocycles described so far (telomestatin-like polyheteroarenes, porphyrins and derivatives, polyammonium cyclophanes), and in addressing both synthetic issues and biological aspects.

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

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.

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

2019 ◽  
Vol 23 (11n12) ◽  
pp. 1195-1215 ◽  
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.

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

2013 ◽  
Vol 634-638 ◽  
pp. 1062-1065 ◽  
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

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

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.

scholarly journals Insights into telomeric G-quadruplex DNA recognition by HMGB1 protein

2019 ◽  
Vol 47 (18) ◽  
pp. 9950-9966 ◽  
Author(s):  
Jussara Amato ◽  
Linda Cerofolini ◽  
Diego Brancaccio ◽  
Stefano Giuntini ◽  
Nunzia Iaccarino ◽  
...  
Keyword(s):  
Biological Effects ◽  
Dna Recognition ◽  
Subcellular Location ◽  
Biological Data ◽  
Telomere Maintenance ◽  
Hmgb1 Protein ◽  
Bent Dna ◽  
Quadruplex Dna ◽  
G Quadruplex ◽  
Negative Tumor

Abstract HMGB1 is a ubiquitous non-histone protein, which biological effects depend on its expression and subcellular location. Inside the nucleus, HMGB1 is engaged in many DNA events such as DNA repair, transcription and telomere maintenance. HMGB1 has been reported to bind preferentially to bent DNA as well as to noncanonical DNA structures like 4-way junctions and, more recently, to G-quadruplexes. These are four-stranded conformations of nucleic acids involved in important cellular processes, including telomere maintenance. In this frame, G-quadruplex recognition by specific proteins represents a key event to modulate physiological or pathological pathways. Herein, to get insights into the telomeric G-quadruplex DNA recognition by HMGB1, we performed detailed biophysical studies complemented with biological analyses. The obtained results provided information about the molecular determinants for the interaction and showed that the structural variability of human telomeric G-quadruplex DNA may have significant implications in HMGB1 recognition. The biological data identified HMGB1 as a telomere-associated protein in both telomerase-positive and -negative tumor cells and showed that HMGB1 gene silencing in such cells induces telomere DNA damage foci. Altogether, these findings provide a deeper understanding of telomeric G-quadruplex recognition by HMGB1 and suggest that this protein could actually represent a new target for cancer therapy.

scholarly journals Selective G-Quadruplex DNA Recognition by a New Class of Designed Cyanines

Molecules ◽  
2013 ◽  
Vol 18 (11) ◽  
pp. 13588-13607 ◽  
Author(s):  
Rupesh Nanjunda ◽  
Eric Owens ◽  
Leah Mickelson ◽  
Tyler Dost ◽  
Ekaterina Stroeva ◽  
...  
Keyword(s):  
Dna Recognition ◽  
Quadruplex Dna ◽  
New Class ◽  
G Quadruplex

pH dependent multifunctional and multiply-configurable logic gate systems based on small molecule G-quadruplex DNA recognition

2013 ◽  
Vol 49 (18) ◽  
pp. 1817 ◽  
Author(s):  
Sudipta Bhowmik ◽  
Rabindra Nath Das ◽  
Bibudha Parasar ◽  
Jyotirmayee Dash
Keyword(s):  
Small Molecule ◽  
Logic Gate ◽  
Dna Recognition ◽  
Quadruplex Dna ◽  
G Quadruplex ◽  
Ph Dependent

Interactions of selected gold(iii) complexes with DNA G quadruplexes

2015 ◽  
Vol 44 (8) ◽  
pp. 3633-3639 ◽  
Author(s):  
P. Gratteri ◽  
L. Massai ◽  
E. Michelucci ◽  
R. Rigo ◽  
L. Messori ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Dna Conformation ◽  
Telomeric Dna ◽  
Quadruplex Dna ◽  
G Quadruplex

The interactions of three Au(iii) complexes with human telomeric DNA sequences: Auoxo6 turned out to be very effective in inducing and binding the G-quadruplex DNA conformation.

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

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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