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-PEG₄, 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.