DNA scission of non-His-containing ATCUN-like peptides

Metallopeptides display interesting candidates for drug design from anti-cancer reagents to antimicrobials. We report the ability of non-His containing metallopeptides to perform scission of plasmid DNA exhibiting antibiotic resistance. The peptides Ac-Dap β Ala His PEG4 with an Amino-Terminal Cu(II) and Ni(II) binding (ATCUN) motif and two mutants, in which His is substituted 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 show specificity to AT-rich DNA regions. Previously, DNA scission was only associated with His-containing ATCUN peptides of other molecular structures. Results from fluorescence displacement of Hoechst 33258 and ethidium bromide show that all three peptides bind to the DNA minor groove and this binding is enhanced in the presence of the bivalent metal ions. Molecular dynamics simulations with a DNA dodecanucleotide d(CGCGAATTCGCG) support the minor groove binding and preference for AT-rich sites for the His and Asp-containing peptides.