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PreprintCC BY-NC-NDChemRxiv

Decoding the Sequence Determinants of DNA Cleavage in Histidine-Containing Copper(II) Metallopeptides

  • Ana B. Caballero1,2,3
  • Olga Iranzo4
  • Patrick Gamez1,5,6
6 affiliations
  1. 1Departament de Química Inorgànica i Orgànica, Facultat de Química, Universitat de Barcelona, Martí i Franquès, 1-11, Barcelona, Spain, 08028
  2. 2Institute of Nanoscience and Nanotechnology (IN2UB
  3. 3Universitat de Barcelona
  4. 4Aix Marseille Univ, CNRS, Centrale Med, iSm2
  5. 5Institute of Biomedicine of the University of Barcelona (IBUB, Avda. Diagonal, 643, Edifici Prevosti, Barcelona, Spain, 08028
  6. 6Passeig Lluís Companys
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Abstract

The increasing global incidence of cancer, emerging viral infections, and antimicrobial resistance highlights the urgent need for innovative therapeutics with novel mechanisms of action. Nucleic acids, central to genetic information processing, are promising targets for therapeutic intervention through selective cleavage. Inspired by the biological activity of DNases and RNases, peptide-based metallonucleases—particularly those containing histidine—have emerged as versatile agents with tunable activity and potential applications in treating genetic diseases, including cancer. By analyzing a set of six copper(II) complexes with different histidine-containing tripeptides, this work investigates how peptide sequence influences several factors determining DNA-cleavage efficiency, such as speciation and conditional affinity at physiological pH, coordination mode, DNA binding, and ROS production. These findings offer a new framework for designing peptide-based copper nucleases and possibly identify a non-ATCUN sequence as a promising lead structure.

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Cite

BibTeXRIS
BibTeX
@misc{caballero2026decoding,
  title = {{Decoding the Sequence Determinants of DNA Cleavage in Histidine-Containing Copper(II) Metallopeptides}},
  author = {Ana B. Caballero and Olga Iranzo and Patrick Gamez},
  howpublished = {ChemRxiv},
  year = {2026},
  month = oct,
  doi = {10.26434/chemrxiv.15009974/v1},
  url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009974/v1},
  note = {CC BY-NC-ND},
}
RIS
TY  - UNPB
TI  - Decoding the Sequence Determinants of DNA Cleavage in Histidine-Containing Copper(II) Metallopeptides
AU  - Ana B. Caballero
AU  - Olga Iranzo
AU  - Patrick Gamez
PY  - 2026
DA  - 2026/10/06
PB  - ChemRxiv
DO  - 10.26434/chemrxiv.15009974/v1
UR  - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009974/v1
AB  - The increasing global incidence of cancer, emerging viral infections, and antimicrobial resistance highlights the urgent need for innovative therapeutics with novel mechanisms of action. Nucleic acids, central to genetic information processing, are promising targets for therapeutic intervention through selective cleavage. Inspired by the biological activity of DNases and RNases, peptide-based metallonucleases—particularly those containing histidine—have emerged as versatile agents with tunable activity and potential applications in treating genetic diseases, including cancer. By analyzing a set of six copper(II) complexes with different histidine-containing tripeptides, this work investigates how peptide sequence influences several factors determining DNA-cleavage efficiency, such as speciation and conditional affinity at physiological pH, coordination mode, DNA binding, and ROS production. These findings offer a new framework for designing peptide-based copper nucleases and possibly identify a non-ATCUN sequence as a promising lead structure.
ER  -