ArticleNucleic acids research2021
Click and Cut: a click chemistry approach to developing oxidative DNA damaging agents.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Rational design of an acridine-derived click chemistry-based artificial metallo-nuclease.RSC chemical biology · 2026Article
- Accessing New Phenanthroline-Oxazine Scaffolds as Copper-Dependent DNA Damaging Probes.Chembiochem : a European journal of chemical biology · 2026Article
- Expanding the DNA damaging potential of artificial metallo-nucleases with click chemistry.Nature communications · 2026Article
- Recent progress in probing small molecule interactions with DNA.Biophysical reviews · 2025Review
- Design and in vitro anticancer assessment of a click chemistry-derived dinuclear copper artificial metallo-nuclease.Nucleic acids research · 2025Article
- Near-Infrared Perylenecarboximide Fluorophores for Live-Cell Super-Resolution Imaging.Journal of the American Chemical Society · 2024Article
- A copper(ii) peptide helicate selectively cleaves DNA replication foci in mammalian cells.Chemical science · 2023Article
- Single-molecule approaches for DNA damage detection and repair: A focus on Repair Assisted Damage Detection (RADD).DNA repair · 2023Review
- Copper(II) and silver(I)-1,10-phenanthroline-5,6-dione complexes interact with double-stranded DNA: further evidence of their apparent multi-modal activity towards Pseudomonas aeruginosa.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2022Article
- Mapping the DNA Damaging Effects of Polypyridyl Copper Complexes with DNA Electrochemical Biosensors.Molecules (Basel, Switzerland) · 2022Article
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Authors and funding
6 authors.
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Abstract
Metallodrugs provide important first-line treatment against various forms of human cancer. To overcome chemotherapeutic resistance and widen treatment possibilities, new agents with improved or alternative modes of action are highly sought after. Here, we present a click chemistry strategy for developing DNA damaging metallodrugs. The approach involves the development of a series of polyamine ligands where three primary, secondary or tertiary alkyne-amines were selected and 'clicked' using the copper-catalysed azide-alkyne cycloaddition reaction to a 1,3,5-azide mesitylene core to produce a family of compounds we call the 'Tri-Click' (TC) series. From the isolated library, one dominant ligand (TC1) emerged as a high-affinity copper(II) binding agent with potent DNA recognition and damaging properties. Using a range of in vitro biophysical and molecular techniques-including free radical scavengers, spin trapping antioxidants and base excision repair (BER) enzymes-the oxidative DNA damaging mechanism of copper-bound TC1 was elucidated. This activity was then compared to intracellular results obtained from peripheral blood mononuclear cells exposed to Cu(II)-TC1 where use of BER enzymes and fluorescently modified dNTPs enabled the characterisation and quantification of genomic DNA lesions produced by the complex. The approach can serve as a new avenue for the design of DNA damaging agents with unique activity profiles.
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