Catalytic and Selective Red Light-Triggered Photodegradation of a G-Quadruplex DNA by a Zinc (II) Phthalocyanine

Chembiochem. 2024 Sep 2;25(17):e202400197. doi: 10.1002/cbic.202400197. Epub 2024 Aug 13.

Abstract

Water-soluble phthalocyanine (Pc) derivatives have been regarded as potential G-quadruplex (G4) nucleic acid-targeting ligands for anticancer therapy and have been extensively studied as effective photosensitizers for photodynamic therapy (PDT). Understanding how photosensitizers interact with nucleic acids and the subsequent photolytic reactions is essential for deciphering the initial steps of PDT, thereby aiding in the development of new photosensitizing agents. In this study, we found that red-light irradiation of a mixture of a Zn(II) Pc derivative and an all-parallel G4 DNA leads to catalytic and selective photodegradation of the DNA by reactive oxygen species (ROS) generated from the Zn(II) Pc derivative bound to DNA through a reaction mechanism similar to that of an enzyme reaction. This finding provides a novel insight into the molecular design of a photosensitizer to enhance its PDT efficacy.

Keywords: G-quadruplex DNA; G-quartet; Molecular recognition; Photodynamic therapy (PDT); Phthalocyanine.

MeSH terms

  • Catalysis
  • DNA* / chemistry
  • G-Quadruplexes* / drug effects
  • Indoles* / chemistry
  • Indoles* / pharmacology
  • Isoindoles*
  • Light*
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacology
  • Photochemotherapy
  • Photolysis* / radiation effects
  • Photosensitizing Agents* / chemistry
  • Photosensitizing Agents* / pharmacology
  • Photosensitizing Agents* / radiation effects
  • Reactive Oxygen Species / metabolism
  • Red Light
  • Zinc / chemistry
  • Zinc / pharmacology
  • Zinc Compounds / chemistry

Substances

  • Indoles
  • Isoindoles
  • Photosensitizing Agents
  • DNA
  • Zn(II)-phthalocyanine
  • Organometallic Compounds
  • Zinc
  • phthalocyanine
  • Zinc Compounds
  • Reactive Oxygen Species