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• W4225535704 abstract "RNA G-quadruplex (GQs) sequences in 5'-UTRs of certain proto-oncogenes co-localize with hairpin (Hp) forming sequences resulting in intramolecular Hp-GQ conformational equilibria, which is suggested to regulate cancer development and progression. Thus, regulation of Hp-GQ equilibria with small molecules is an attractive but less explored therapeutic approach. Herein, two tetraphenylethene (TPE) derivatives, TPE-Py and TPE-MePy, were synthesized and their effect on Hp-GQ equilibrium was explored. FRET, CD and molecular docking experiments suggest that cationic TPE-MePy shifts the Hp-GQ equilibrium significantly towards the GQ conformer mainly through π-π stacking and van der Waals interactions. In the presence of TPE-MePy, the observed rate constant values for first and second folding steps were increased up to 14.6 and 2.6-fold, respectively. The FRET melting assay showed a strong stabilizing ability of TPE-MePy (ΔTm=4.36 °C). Notably, the unmethylated derivative TPE-Py did not alter the Hp-GQ equilibrium. Subsequently, luciferase assay analysis demonstrated that the TPE-MePy derivatives suppressed the translation efficiency by ∼5.7-fold by shifting the Hp-GQ equilibrium toward GQ conformers in the 5'-UTR of TRF2. Our data suggests that HpGQ equilibria could be selectively targeted with small molecules to modulate translation for therapy." @default.
• W4225535704 created "2022-05-05" @default.
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• W4225535704 date "2022-05-11" @default.
• W4225535704 modified "2023-09-27" @default.
• W4225535704 title "Tetraphenylethene Derivatives Modulate the RNA Hairpin‐G‐Quadruplex Conformational Equilibria in Proto‐oncogenes**" @default.
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• W4225535704 doi "https://doi.org/10.1002/cbic.202200131" @default.
• W4225535704 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35467068" @default.
• W4225535704 hasPublicationYear "2022" @default.
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