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Single-molecule Manipulation of G-quadruplexes by Magnetic Tweezers
Published on: September 19, 2017
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Short designed peptide unfolding human telomeric G-quadruplex: mimicking the helicase function
Taniya Sharma1, Nikita Kundu1, Sarvpreet Kaur1
1Amity Institute of Biotechnology, Amity University Uttar Pradesh, Noida, India.
Journal of Biomolecular Structure & Dynamics
|November 28, 2022
Summary
A novel peptide, QW5, destabilizes human telomeric G-quadruplex (G4) structures. This G4 unfolding by QW5 peptide shows potential for targeting diseases with G4 motif over-representation.
Area of Science:
- Biochemistry
- Molecular Biology
- Genetics
Background:
- Human telomeric DNA can form G-quadruplex (G4) structures, which are implicated in various diseases.
- G4 topologies present unique therapeutic targets due to their distinctive nature.
Purpose of the Study:
- To investigate the destabilization of human telomeric G-quadruplex structures by peptide binding.
- To evaluate the therapeutic potential of a specific peptide (QW5) in targeting G4 motifs.
Main Methods:
- Circular dichroism (CD) spectroscopy to analyze G4 folding and peptide interaction.
- UV-thermal melting to assess G4-peptide complex formation.
- Fluorescence spectroscopy and electrophoretic mobility shift assay (EMSA) to confirm G4 unfolding.
Main Results:
- Peptide binding significantly decreased CD intensity and hypochromicity, indicating G4 destabilization.
- Fluorescence quenching and EMSA confirmed QW5 peptide's ability to unfold human telomeric G-quadruplex.
- QW5 peptide demonstrated significant cytotoxicity, reducing cell viability with low IC50 values.
Conclusions:
- The QW5 peptide effectively binds and unfolds human telomeric G-quadruplex structures.
- QW5 peptide is a potential therapeutic modulator for diseases characterized by G4 motif over-representation.
- Destabilization of G4 structures may enhance DNA replication, transcription, or duplex reannealing.
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