Tuning redox and biological activity of Cu(II) metallopeptide

ATCUN (aminoterminal Cu(II) and Ni(II)-binding) metallopeptides have been designed

and applied for different purposes comprising e.g. hydrogen evolution from water[1]

and antitumor drug treatment.[2] The redox activity of these complexes usually plays

a decisive role for such activities.

The Cu(II) complex of the most simple peptide motif Gly-Gly-His (GGH) has

surprisingly been proven to be almost redox inert.[3] In order to restore this redox

activity and also obtain additional functionalities, we incorporated fluorophores for

sensing Cu(II) ions[4] and artificial b-amino acids for influencing the chelate ring size

and thus stability, redox activity and even cytotoxicity of the Cu(II) peptides.[5]

Incorporation of N-heteroaromatics into the peptide ligand scaffold, e.g. a pyridine

moiety, led to an increased production of reactive oxygen species (ROS) from O2,

which were shown to be able to degrade DNA.[6] Conjugation with a targeting peptide

allowed selective cytotoxicity in cancer cells.