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.

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 G-Quadruplex Binding Properties of A Potent PARP-1 Inhibitor Derived From 7-Azaindole-1-Carboxamide

2020 ◽  
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

Abstract Poly 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.

The effect of isomerism and other structural variations on the G-quadruplex DNA-binding properties of some nickel Schiff base complexes

2020 ◽  
Vol 49 (30) ◽  
pp. 10360-10379 ◽  
Author(s):  
Son Q. T. Pham ◽  
Christopher Richardson ◽  
Celine Kelso ◽  
Anthony C. Willis ◽  
Stephen F. Ralph
Keyword(s):  
Schiff Base ◽  
Dna Binding ◽  
Schiff Base Complexes ◽  
Structural Variations ◽  
Binding Properties ◽  
Quadruplex Dna ◽  
G Quadruplex ◽  
Dna Binding Properties ◽  
Binding Behaviour

Changing the position of pendant groups on nickel Schiff base complexes can alter their binding behaviour towards quadruplex DNA.

scholarly journals Development of an Illumina-based ChIP-exonuclease method provides insight into FoxA1-DNA binding properties

2013 ◽  
Vol 14 (12) ◽  
pp. R147 ◽  
Author(s):  
Aurelien A Serandour ◽  
Gordon D Brown ◽  
Joshua D Cohen ◽  
Jason S Carroll
Keyword(s):  
Dna Binding ◽  
Binding Properties ◽  
Dna Binding Properties ◽  
Insight Into

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

2018 ◽  
Vol 42 (7) ◽  
pp. 4933-4939 ◽  
Author(s):  
Ming-Qi Wang ◽  
Xiao-Ning Liu ◽  
Zhong-Jian Guo ◽  
Chunlai Feng ◽  
Mengjie Rui
Keyword(s):  
Docking Studies ◽  
Binding Properties ◽  
Quadruplex Dna ◽  
Dna Targeting ◽  
G Quadruplex

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

scholarly journals Alkaloid Escholidine and Its Interaction with DNA Structures

Biology ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1225
Author(s):  
Petra Jarošová ◽  
Pavel Hannig ◽  
Kateřina Kolková ◽  
Stefania Mazzini ◽  
Eva Táborská ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Binding ◽  
Binding Properties ◽  
Dna Structures ◽  
Xiap Expression ◽  
G Quadruplex ◽  
Kit Gene ◽  
Myc Gene ◽  
Dna Binding Properties ◽  
Protoberberine Alkaloid

Berberine, the most known quaternary protoberberine alkaloid (QPA), has been reported to inhibit the SIK3 protein connected with breast cancer. Berberine also appears to reduce the bcl-2 and XIAP expression-proteins responsible for the inhibition of apoptosis. As some problems in the therapy with berberine arose, we studied the DNA binding properties of escholidine, another QPA alkaloid. CD, fluorescence, and NMR examined models of i-motif and G-quadruplex sequences present in the n-myc gene and the c-kit gene. We provide evidence that escholidine does not induce stabilization of the i-motif sequences, while the interaction with G-quadruplex structures appears to be more significant.

scholarly journals Synthesis of 10-O-aryl-substituted berberine derivatives by Chan–Evans–Lam coupling and investigation of their DNA-binding properties

2021 ◽  
Vol 17 ◽  
pp. 991-1000
Author(s):  
Peter Jonas Wickhorst ◽  
Mathilda Blachnik ◽  
Denisa Lagumdzija ◽  
Heiko Ihmels
Keyword(s):  
Dna Binding ◽  
Coupling Reaction ◽  
Spectroscopic Studies ◽  
Binding Properties ◽  
Quadruplex Dna ◽  
G4 Dna ◽  
Fluorescence Light ◽  
Berberine Derivatives ◽  
Ct Dna ◽  
Dna Binding Properties

Eleven novel 10-O-aryl-substituted berberrubine and berberine derivatives were synthesized by the Cu2+-catalyzed Chan–Evans–Lam coupling of berberrubine with arylboronic acids and subsequent 9-O-methylation. The reaction is likely introduced by the Cu2+-induced demethylation of berberrubine and subsequent arylation of the resulting 10-oxyanion functionality. Thus, this synthetic route represents the first successful Cu-mediated coupling reaction of berberine substrates. The DNA-binding properties of the 10-O-arylberberine derivatives with duplex and quadruplex DNA were studied by thermal DNA denaturation experiments, spectrometric titrations as well as CD and LD spectroscopy. Fluorimetric DNA melting analysis with different types of quadruplex DNA revealed a moderate stabilization of the telomeric quadruplex-forming oligonucleotide sequence G3(TTAG3)3. The derivatives showed a moderate affinity towards quadruplex DNA (K b = 5–9 × 105 M−1) and ct DNA (K b = 3–5 × 104 M−1) and exhibited a fluorescence light-up effect upon complexation to both DNA forms, with slightly higher intensity in the presence of the quadruplex DNA. Furthermore, the CD- and LD-spectroscopic studies revealed that the title compounds intercalate into ct DNA and bind to G4-DNA by terminal stacking.

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