Thiazole Containing PNA Mimic Regulates <i>c-MYC</i> Gene Expression through DNA G-Quadruplex

Gorai, Ananta; Chaudhuri, Ritapa; Mukhopadhyay, Titas Kumar; Datta, Ayan

doi:10.1021/acs.bioconjchem.2c00075

Cited by 3 publications

(1 citation statement)

References 65 publications

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“…However, this binding mode makes it problematic to discriminate among different G4 structures. In this regard, different approaches to gain selectivity have recently started to be explored, such as ligand–peptide conjugates, simultaneous recognition of duplex and quadruplex motifs, , a DNA molecule that hybridize with the flanking single strand to target RNA G4s, peptide nucleic acid (PNA) derivatives, − and ligand-PNA conjugates. , However, the slow progression of selective individual G4 targeting methods highlights the need for diverse approaches.…”

Section: Introductionmentioning

confidence: 99%

G4-Ligand-Conjugated Oligonucleotides Mediate Selective Binding and Stabilization of Individual G4 DNA Structures

Berner,

Das,

Bhuma

et al. 2024

J. Am. Chem. Soc.

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G-quadruplex (G4) DNA structures are prevalent secondary DNA structures implicated in fundamental cellular functions, such as replication and transcription. Furthermore, G4 structures are directly correlated to human diseases such as cancer and have been highlighted as promising therapeutic targets for their ability to regulate disease-causing genes, e.g., oncogenes. Small molecules that bind and stabilize these structures are thus valuable from a therapeutic perspective and helpful in studying the biological functions of the G4 structures. However, there are hundreds of thousands of G4 DNA motifs in the human genome, and a long-standing problem in the field is how to achieve specificity among these different G4 structures. Here, we developed a strategy to selectively target an individual G4 DNA structure. The strategy is based on a ligand that binds and stabilizes G4s without selectivity, conjugated to a guide oligonucleotide, that specifically directs the G4-Ligand-conjugated oligo (GL-O) to the single target G4 structure. By employing various biophysical and biochemical techniques, we show that the developed method enables the targeting of a unique, specific G4 structure without impacting other off-target G4 formations. Considering the vast amount of G4s in the human genome, this represents a promising strategy to study the presence and functions of individual G4s but may also hold potential as a future therapeutic modality.

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Section: Introductionmentioning

confidence: 99%

G4-Ligand-Conjugated Oligonucleotides Mediate Selective Binding and Stabilization of Individual G4 DNA Structures

Berner,

Das,

Bhuma

et al. 2024

J. Am. Chem. Soc.

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Synthesis of Substituted Arylidene Hydrazinyl Trifluoromethyl Thiazole Derivatives and their Antibacterial Studies using different Genes Expression

Abed,

Abid,

Turki

et al. 2024

ChemistrySelect

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Cyclization of substituted thiosemicarbazones with 3‐bromo‐1,1,1‐trifluoroacetone affords new 2‐(arylidenehydrazinyl)‐4‐trifluoromethylthiazoles (3 a–m, 13 examples, 71–89 %). These compounds were synthesized in two steps and characterized using 1H‐, 13C‐NMR, FTIR spectroscopy, and HRMS. All of these compounds show potent activity against both Escherichia coli (E. coli) and Klebsiella pneumonia (K. pneumonia) bacterial strains. The compounds 2‐(2‐(1‐(4‐fluorophenyl)ethylidene)hydrazinyl)‐4(trifluoromethyl)thiazole (3 b), 2‐(2‐(2‐hydroxy‐3‐methylbenzylidene)hydrazinyl)‐4‐(trifluoromethyl)thiazole (3 c), and 2‐(2‐(3‐fluorobenzylidene)hydrazinyl)‐4‐(trifluoromethyl)thiazole (3 k) show optimal minimum inhibitory concentration (MIC) values of 16 μg/mL against E. coli and (32, 32, and 8 μg/ml) against K. pneumonia, respectively. Using a qRT‐PCR technique the gene expression of two different genes (FLU and mexB) was determined. Most of these compounds (3 a, d–j, l, m) exhibited downregulation of these genes for both types of bacteria, whereas the gene expressions were unaffected after treating 3 b, 3 c and 3 k. This means that although these compounds were able to inhibit bacterial growth, they did not target the FLU and mexB genes in both types of bacteria. These findings suggest further investigations for lead optimization could provide viable antibiotics due to their structural similarity with some commercially available antibiotics.

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Ultrasound-assisted Peptide Nucleic Acids synthesis (US-PNAS)

Bene

D'Aniello

Tomassi

et al. 2023

Ultrasonics Sonochemistry

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Thiazole Containing PNA Mimic Regulates c-MYC Gene Expression through DNA G-Quadruplex

Cited by 3 publications

References 65 publications

G4-Ligand-Conjugated Oligonucleotides Mediate Selective Binding and Stabilization of Individual G4 DNA Structures

G4-Ligand-Conjugated Oligonucleotides Mediate Selective Binding and Stabilization of Individual G4 DNA Structures

Synthesis of Substituted Arylidene Hydrazinyl Trifluoromethyl Thiazole Derivatives and their Antibacterial Studies using different Genes Expression

Ultrasound-assisted Peptide Nucleic Acids synthesis (US-PNAS)

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