Doxorubicin exhibits strong and selective association with VEGF Pu22 G-quadruplex

Bilgen, Ecenaz; Çetinkol, Özgül Persil

doi:10.1016/j.bbagen.2020.129720

Cited by 14 publications

(7 citation statements)

References 47 publications

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“…7 b,c). This increase in the fluorescence was comparable to that observed with the Pu 22 sequence (F-F 0 = 495 ± 13) present in the promoter region of the VEGF (vascular epithelial growth factor) gene, which was previously characterized to form a G4 structure 80 , 81 . These together with low fluorescence intensities of ThT at 488 nm with various mutant sequences of SegC-G4 designed to disrupt the G4 formation (SegC-Mut1-3), SegC complementary (SegC-Comp), or dT 32 suggest the possible adaptation of a G4 structure by SegC-G4 sequence.…”

Section: Resultssupporting

confidence: 83%

A CpG island promoter drives the CXXC5 gene expression

Yaşar

Kars

Yavuz

et al. 2021

Sci Rep

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CXXC5 is a member of the zinc-finger CXXC family that binds to unmethylated CpG dinucleotides. CXXC5 modulates gene expressions resulting in diverse cellular events mediated by distinct signaling pathways. However, the mechanism responsible for CXXC5 expression remains largely unknown. We found here that of the 14 annotated CXXC5 transcripts with distinct 5′ untranslated regions encoding the same protein, transcript variant 2 with the highest expression level among variants represents the main transcript in cell models. The DNA segment in and at the immediate 5′-sequences of the first exon of variant 2 contains a core promoter within which multiple transcription start sites are present. Residing in a region with high G–C nucleotide content and CpG repeats, the core promoter is unmethylated, deficient in nucleosomes, and associated with active RNA polymerase-II. These findings suggest that a CpG island promoter drives CXXC5 expression. Promoter pull-down revealed the association of various transcription factors (TFs) and transcription co-regulatory proteins, as well as proteins involved in histone/chromatin, DNA, and RNA processing with the core promoter. Of the TFs, we verified that ELF1 and MAZ contribute to CXXC5 expression. Moreover, the first exon of variant 2 may contain a G-quadruplex forming region that could modulate CXXC5 expression.

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Section: Resultssupporting

confidence: 83%

A CpG island promoter drives the CXXC5 gene expression

Yaşar

Kars

Yavuz

et al. 2021

Sci Rep

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“…Herein, we used in vitro selected G-quadruplex DNA sequence (G4-DNA-DOX, 5′-CGGGGCGGGCCGGGGGCGGGGT-3′), which acted as an aptamer to bind DOX effectively . As illustrated in Figure S40, the UV–vis absorption spectrum demonstrates a decrease in the peak at 500 nm, indicating the interaction between DOX and the DNA component. , Upon the addition of Cu 2+ , a red-shift occurs, accompanied by the emergence of a new peak at 585 nm, indicative of the formation of the DOX/G4-DNA-DOX/Cu 2+ complex . Furthermore, upon the introduction of Fmoc-K, only a slight alteration in the spectrum is observed, suggesting that the structure of the DOX/G4-DNA-DOX/Cu 2+ complex was retained.…”

Section: Resultsmentioning

confidence: 99%

“…The folding characteristics of the G-quadruplex structures not only facilitated the copper catalysis, but also enabled interactions of the catalyst with specific small molecules, such as the anticancer drug doxorubicin. 26 Consequently, the enzyme mimic could be employed for catalyzing the degradation of pharmaceutical pollutants. Furthermore, the DNA component exhibited the capability to undergo conformational changes triggered by photoirradiation, which enables the photostimulated control of catalyst activity.…”

Section: Introductionmentioning

confidence: 99%

“…It was discovered that the DNA/Fmoc-K/Cu 2+ aggregates exhibited higher catalytic kinetics to laccase (a catechol oxidase known for its superior activity) based on molecular mass, and also great stability against elevated temperature, high ionic strength, and storage conditions. The folding characteristics of the G-quadruplex structures not only facilitated the copper catalysis, but also enabled interactions of the catalyst with specific small molecules, such as the anticancer drug doxorubicin . Consequently, the enzyme mimic could be employed for catalyzing the degradation of pharmaceutical pollutants.…”

Section: Introductionmentioning

confidence: 99%

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Self-Assembled G-fold DNA/Amino Acid Amphiphiles-Based Oxidase-Mimetic Materials Exhibiting Drug-Degrading and Photoswitchable Capabilities

Xu,

Wu,

Liu

et al. 2024

Chem. Mater.

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Recreating the intricate enzymatic sites within in artificial materials poses a significant challenge due to the complex folding characteristics of enzymes. In this study, we designed a supramolecular catalyst by assembling intramolecularly folding Gquadruplex DNA with Fmoc-amino acid aggregates and Cu 2+ . This supramolecular material possesses active sites and catalytic functions that rely on copper clusters, mirroring the functionality of catechol oxidase. Experimental and theoretical simulations showed that Fmoc-amino acids interact with G-quadruplex DNA through groove binding, facilitating Cu 2+ coordination to both components, thereby enhancing the oxidative catalysis of Cu 2+ upon assembly. Our catalyst exhibited excellent tolerance to high temperature, varying ionic strength, and extended room-temperature storage in aqueous solutions. Moreover, our supramolecular complex effectively catalyzed the degradation of doxorubicin, a drug with a high affinity for the DNA component, demonstrating its potential for removing pharmacological pollutants. Additionally, by integrating a photoisomerizable azobenzene derivative as a ligand to the G-quadruplex DNA, we can switch the activity of the enzyme-mimetic catalyst between on and off states by adjusting the irradiation wavelength. This multicomponent approach offers a promising avenue for the design and engineering of active, adaptable supramolecular catalysts.

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“…G4 has a variety of sites that small molecules can recognize. Further, several small molecules have been suggested to be binders and stabilizers of G4 in vitro experiments. − However, many small molecules are limited to further development due to their poor druglike properties …”

Section: Introductionmentioning

confidence: 99%

Characterization of the Binding Properties of Sorafenib to c-MYC G-Quadruplexes: Evidence for Screening Potential Ligands

Zeng

et al. 2023

J. Phys. Chem. B

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Sorafenib (Sor) is a multitarget kinase inhibitor used clinically to treat hepatocellular carcinoma and renal cancer. In this study, the interaction mechanism of Sor with c-MYC Gquadruplexes (G4) was investigated at the molecular level by computer-aided means and experiments. Molecular docking results predicted the binding of Sor to the groove of G4. Molecular dynamics (MD) simulations were used to evaluate the effect of ligand binding to G4. Ultraviolet (UV), fluorescence spectroscopy, and viscosity experiments showed that the binding site was in the groove. The UV and fluorescence titration results showed that compared with traditional G4 ligands represented by compound meso-tetra (N-methyl-4-pyridyl) porphine (TmPyP4), Sor has a lower affinity for G4. Likewise, results from fluorescence resonance energy transfer (FRET) experiments suggested that Sor could have a limited ability to stabilize G4, but it was not as prominent as that of TmPyP4. Time-resolved fluorescence spectroscopy again supported the results from steady-state fluorescence spectroscopy, indicating that a static quenching mechanism mainly drove the process. Studying the interaction mechanism of Sor and c-MYC may inspire the screening of new, selective c-MYC G4 ligands and provide ideas for the design of drugs with good stability, low toxicity, and specific targeting of G4.

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Doxorubicin exhibits strong and selective association with VEGF Pu22 G-quadruplex

Cited by 14 publications

References 47 publications

A CpG island promoter drives the CXXC5 gene expression

A CpG island promoter drives the CXXC5 gene expression

Self-Assembled G-fold DNA/Amino Acid Amphiphiles-Based Oxidase-Mimetic Materials Exhibiting Drug-Degrading and Photoswitchable Capabilities

Characterization of the Binding Properties of Sorafenib to c-MYC G-Quadruplexes: Evidence for Screening Potential Ligands

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