DNA Scission by Non‐Histidine Amino‐Terminal Cu(II) and Ni(II) Binding‐Like Peptides

Metallopeptides are promising candidates for drug design, ranging from anticancer agents to antimicrobials. We report the ability of non‐His‐containing metallopeptides to induce scission of plasmid DNAs that carry antibiotic resistance genes. The peptide Ac‐Dap‐β‐Ala‐His‐PEG 4 , featuring an amino‐terminal Cu(II) and Ni(II) binding (ATCUN) motif, along with two mutants where His is replaced by Ala and Asp, form complexes with Cu(II) and Ni(II) in a pH‐dependent manner, attributed to metal coordination. The His‐ and Asp‐containing peptides demonstrate specificity for AT‐rich DNA regions. Previously, DNA scission was exclusively associated with His‐containing ATCUN peptides of other molecular structures.