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Reversible Redox Controlled DNA Condensation by a Simple Noncanonical Dicationic Diphenylalanine Derivative.

Ana M Bernal-Martínez1, César A Angulo-Pachón1,2, Francisco Galindo1

  • 1Departmento de Química Inorgánica y Orgánica, Universidad Jaume I, Castellón, Spain.

Biopolymers
|January 28, 2025
PubMed
Summary

This study presents a novel dicationic molecule for reversible DNA condensation. This non-canonical agent uses redox-sensitive disulfide bonds for controlled DNA binding and release, enabling dynamic manipulation.

Keywords:
DNA condensationaromatic peptidesdynamic light scatteringredox‐responsive systemsstimuli‐controlled aggregation

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Area of Science:

  • Biochemistry
  • Materials Science
  • Molecular Biology

Background:

  • DNA condensation is crucial for gene delivery and nanotechnology.
  • Conventional DNA condensing agents typically require a charge of +3 or higher.
  • Developing stimuli-responsive DNA binding agents is an active research area.

Purpose of the Study:

  • To introduce a novel dicationic molecule for reversible, redox-controlled DNA condensation.
  • To demonstrate that a dicationic molecule can function as a DNA condensing agent below its critical aggregation concentration.
  • To explore the combined electrostatic and hydrophobic interactions in DNA binding.

Main Methods:

  • Synthesis of a dicationic diphenylalanine derivative with a disulfide linker.
  • DNA condensation and decondensation assays.
  • Characterization using Thioflavin T (ThT) displacement, circular dichroism (CD), 1H Nuclear Magnetic Resonance (NMR), and dynamic light scattering (DLS).

Main Results:

  • The dicationic molecule successfully condensed DNA, functioning as a non-canonical condensing agent.
  • Redox-induced cleavage of the disulfide bond led to DNA decondensation.
  • Oxidation reversed the process, restoring DNA condensation.
  • Multiple techniques confirmed the reversible redox-controlled DNA manipulation.

Conclusions:

  • A simple dicationic molecule can reversibly control DNA condensation via redox stimuli.
  • This offers a new strategy for dynamic DNA manipulation in various applications.
  • The findings challenge conventional understanding of DNA condensing agents.